CompuCell3DAttachment 'BIOMD0000000619.xml'
Download 1 <?xml version='1.0' encoding='UTF-8' standalone='no'?>
2
3 <!-- This model was downloaded from BioModels Database -->
4 <!-- Wed Jul 26 21:02:55 BST 2017 -->
5 <!-- http://www.ebi.ac.uk/biomodels/ -->
6
7 <sbml xmlns="http://www.sbml.org/sbml/level2/version4" level="2" metaid="c67e6fe0-8c83-40a9-a85f-76f619b9950c" version="4">
8 <model id="MODEL1509230010" metaid="_Sluka0000" name="Sluka2016 - Acetaminophen PBPK" sboTerm="SBO:0000167">
9 <notes>
10 <body xmlns="http://www.w3.org/1999/xhtml">
11 <h1>Basic PBPK (Physiologically Based PharmacoKinetic) model of Acetaminophen.</h1>
12 <p>This is a basic model of Acetaminophen (APAP, Paracetamol) pharmacokinetics in humans. Many of the model parameters
13 (compartment volumes, volumetric flow rates, etc.) are scaled allometrically based on the body weight (BW) raised to the
14 3/4 power. Because of that, the assigned values of many of the parameters are recalculated at run time and are different
15 than the default values for the particular entity (e.g., the volume of a compartment and the volumetric flow rate between compartments).</p>
16 <p>APAP dose is initially given in grams (APAP_Dose_gram), which is converted to moles via the APAP molecular weight (APAP_MW).
17 APAP quantities throughout the rest of the models are given in moles.</p>
18 <p>The base parameters are for a 70Kg human and a pharmacological oral dose of 1.4 gram of APAP. Metabolism is modelled as a single ODE in the liver compartment and the metabolite does not leave that compartment.</p>
19 <p>This model is loosely based on the model of Wambaugh and Shaw (PLoS Comput Biol. 2010 Apr 22;6(4):e1000756. doi: 10.1371/journal.pcbi.1000756. Pubmed ID: PMID- 20421935) with the following changes:</p>
20 <ol> <li>The lung lumen compartment was omitted.</li>
21 <li>A kidney compartment was added.</li>
22 <li>Glomerular Filtration is from the kidney compartment.</li>
23 <li>The APAP dose was changed to 1.4g.</li>
24 <li>The gut adsorption rate constant (KGutabs), tissue partition coefficients and liver metabolism rate constant (CLmetabolism) were fit using the human <i>in vivo</i>
25 data of Critchley (Critchley, J. A., Critchley, L. A. H., Anderson, P. J., and Tomlinson, B. 2005 Journal of clinical pharmacy and therapeutics, 30(2), 179-184). </li>
26 <li> <b>To model the extensive re-adsorption of APAP from the kidney tubules back into the blood the QGfr value is modified. This was done by
27 changing the scaling parameter QGFR_ref value from 0.31 to 0.039, resulting in a decrease in the QGfr value of 8 fold (from 7.2 L/hr to 0.91 L/hr).</b>
28 </li>
29 </ol>
30 <p>The parameters in this file are the <b>REFSIM</b>
31 parameters from our publication. </p>
32 </body>
33
34 </notes>
35 <annotation>
36 <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/">
37 <rdf:Description rdf:about="#_Sluka0000">
38 <dc:creator>
39 <rdf:Bag>
40 <rdf:li rdf:parseType="Resource">
41 <vCard:N rdf:parseType="Resource">
42 <vCard:Family>Chelliah</vCard:Family>
43 <vCard:Given>Vijayalakshmi</vCard:Given>
44 </vCard:N>
45 <vCard:EMAIL>viji@ebi.ac.uk</vCard:EMAIL>
46 <vCard:ORG rdf:parseType="Resource">
47 <vCard:Orgname>EMBL-EBI</vCard:Orgname>
48 </vCard:ORG>
49 </rdf:li>
50
51 <rdf:li rdf:parseType="Resource">
52 <vCard:N rdf:parseType="Resource">
53 <vCard:Family>Sluka</vCard:Family>
54 <vCard:Given>James</vCard:Given>
55 </vCard:N>
56 <vCard:EMAIL>JSluka@indiana.edu</vCard:EMAIL>
57 <vCard:ORG rdf:parseType="Resource">
58 <vCard:Orgname>Indiana University</vCard:Orgname>
59 </vCard:ORG>
60 </rdf:li>
61 <rdf:li rdf:parseType="Resource">
62 <vCard:N rdf:parseType="Resource">
63 <vCard:Family>Fu</vCard:Family>
64 <vCard:Given>Xiao</vCard:Given>
65 </vCard:N>
66 <vCard:EMAIL>fuxiao@umail.iu.edu</vCard:EMAIL>
67 <vCard:ORG rdf:parseType="Resource">
68 <vCard:Orgname>Indiana University</vCard:Orgname>
69 </vCard:ORG>
70 </rdf:li>
71 </rdf:Bag>
72 </dc:creator>
73 <dcterms:created rdf:parseType="Resource">
74 <dcterms:W3CDTF>2015-02-04T11:47:58Z</dcterms:W3CDTF>
75 </dcterms:created>
76 <dcterms:modified rdf:parseType="Resource">
77 <dcterms:W3CDTF>2017-05-23T10:32:07Z</dcterms:W3CDTF>
78 </dcterms:modified>
79 <bqmodel:is>
80 <rdf:Bag>
81 <rdf:li rdf:resource="urn:miriam:biomodels.db:MODEL1509230010"/>
82 </rdf:Bag>
83 </bqmodel:is>
84 <bqmodel:is>
85 <rdf:Bag>
86 <rdf:li rdf:resource="urn:miriam:biomodels.db:BIOMD0000000619"/>
87 </rdf:Bag>
88 </bqmodel:is>
89 <bqmodel:isDescribedBy>
90 <rdf:Bag>
91 <rdf:li rdf:resource="urn:miriam:pubmed:27636091"/>
92 </rdf:Bag>
93 </bqmodel:isDescribedBy>
94 <bqmodel:isDerivedFrom>
95 <rdf:Bag>
96 <rdf:li rdf:resource="urn:miriam:pubmed:20421935"/>
97 </rdf:Bag>
98 </bqmodel:isDerivedFrom>
99 <bqbiol:isVersionOf>
100 <rdf:Bag>
101 <rdf:li rdf:resource="urn:miriam:go:GO%3A0042910"/>
102 <rdf:li rdf:resource="urn:miriam:go:GO%3A0017144"/>
103 </rdf:Bag>
104 </bqbiol:isVersionOf>
105 <bqbiol:hasTaxon>
106 <rdf:Bag>
107 <rdf:li rdf:resource="urn:miriam:taxonomy:9606"/>
108 </rdf:Bag>
109 </bqbiol:hasTaxon>
110 <bqbiol:hasProperty>
111 <rdf:Bag>
112 <rdf:li rdf:resource="urn:miriam:mamo:MAMO_0000203"/>
113 </rdf:Bag>
114 </bqbiol:hasProperty>
115 </rdf:Description>
116
117
118
119 </rdf:RDF>
120 </annotation>
121 <listOfUnitDefinitions>
122 <unitDefinition id="time" metaid="a39afea2-bc11-4099-b184-59a541dd239e" name="hour">
123 <listOfUnits>
124 <unit kind="second" metaid="_84763089-051b-4b08-879d-49d18e149073" multiplier="3600"/>
125 </listOfUnits>
126 </unitDefinition>
127 <unitDefinition id="first_order_rate_constant" metaid="_8978a697-2334-4f0a-a7e0-ced09539242d" name="first_order_rate_constant">
128 <listOfUnits>
129 <unit exponent="-1" kind="second" metaid="_46c09596-a08f-4d7e-80da-b56aac2b066c" multiplier="3600"/>
130 </listOfUnits>
131 </unitDefinition>
132 <unitDefinition id="Volumetric_Flow" metaid="_7d6232bd-6915-4fe3-993d-be552a5829f4" name="Volumetric_Flow">
133 <listOfUnits>
134 <unit kind="litre" metaid="_5c23ea8f-a30c-4b0f-9892-a21f3562a1c1"/>
135 <unit exponent="-1" kind="second" metaid="a36fb4d5-3d04-4a38-ba8c-ebd14bdc748a" multiplier="3600"/>
136 </listOfUnits>
137 </unitDefinition>
138 <unitDefinition id="volume" metaid="ff5f8d83-88e1-4852-9044-44081f09c4df" name="litre">
139 <listOfUnits>
140 <unit exponent="1" kind="litre" metaid="_9e9d6a71-9c01-46c7-b7c8-3134e17ebb5f" multiplier="1"/>
141 </listOfUnits>
142 </unitDefinition>
143 <unitDefinition id="substance" metaid="_86117411-52e3-432f-a962-4aeb22602b84" name="mole">
144 <listOfUnits>
145 <unit exponent="1" kind="mole" metaid="_87cd2160-6057-4a00-859a-313af79fca94"/>
146 </listOfUnits>
147 </unitDefinition>
148 <unitDefinition id="grams2mol" metaid="b02251d1-de38-4130-8740-4772259178b2" name="grams2mol">
149 <notes>
150 <body xmlns="http://www.w3.org/1999/xhtml">
151 <p>Units of molecular weight: grams/mole</p>
152 </body>
153
154 </notes>
155 <listOfUnits>
156 <unit exponent="1" kind="gram" metaid="d19cbd99-94f7-466b-b3fd-73e71a4db75c"/>
157 <unit exponent="-1" kind="mole" metaid="fcfa1f3a-bebf-4199-8d6d-aeb3fd3c8c36"/>
158 </listOfUnits>
159 </unitDefinition>
160 <unitDefinition id="BW_ref" metaid="aeae1f60-930c-468f-9d97-c0e24034f7d9" name="BW_ref">
161 <notes>
162 <body xmlns="http://www.w3.org/1999/xhtml">
163 <p>Reference body weight (Kg) for allometric scaling.</p>
164 </body>
165
166 </notes>
167 <listOfUnits>
168 <unit exponent="1" kind="kilogram" metaid="_46fb9e92-7d58-480d-bd59-aa228bd5fc77"/>
169 </listOfUnits>
170 </unitDefinition>
171 </listOfUnitDefinitions>
172 <listOfCompartmentTypes>
173 <compartmentType id="ORGAN" metaid="_Sluka0401" sboTerm="SBO:0000290">
174 <notes>
175 <body xmlns="http://www.w3.org/1999/xhtml">
176 <p>Compartments such as the liver, lungs, kidneys, ...</p>
177 </body>
178
179 </notes>
180 </compartmentType>
181 <compartmentType id="CIRCULATORY" metaid="_Sluka0402" sboTerm="SBO:0000290">
182 <notes>
183 <body xmlns="http://www.w3.org/1999/xhtml">
184 <p>Blood only compartments such as the arteries and veins.</p>
185 </body>
186
187 </notes>
188 </compartmentType>
189 <compartmentType id="LUMEN" metaid="_Sluka0403" sboTerm="SBO:0000290">
190 <notes>
191 <body xmlns="http://www.w3.org/1999/xhtml">
192 <p>Lumen compartments such as in the lungs, gut and kidney.</p>
193 </body>
194
195 </notes>
196 </compartmentType>
197 </listOfCompartmentTypes>
198 <listOfSpeciesTypes>
199 <speciesType id="APAP" metaid="_Sluka0100" sboTerm="SBO:0000247">
200 <notes>
201 <body xmlns="http://www.w3.org/1999/xhtml">
202 <p>Acetaminophen in all locations.</p>
203 </body>
204
205 </notes>
206 <annotation>
207 <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/">
208 <rdf:Description rdf:about="#_Sluka0100">
209 <bqbiol:is>
210 <rdf:Bag>
211 <rdf:li rdf:resource="urn:miriam:chebi:CHEBI%3A46195"/>
212 </rdf:Bag>
213 </bqbiol:is>
214 </rdf:Description>
215
216
217
218
219 </rdf:RDF>
220 </annotation>
221 </speciesType>
222 <speciesType id="METAB" metaid="_Sluka0101" sboTerm="SBO:0000247">
223 <notes>
224 <body xmlns="http://www.w3.org/1999/xhtml">
225 <p>All metabolites of APAP in all locations.</p>
226 </body>
227
228 </notes>
229 </speciesType>
230 </listOfSpeciesTypes>
231 <listOfCompartments>
232 <compartment compartmentType="CIRCULATORY" constant="true" id="VArt" metaid="_Sluka0001" name="VArt" sboTerm="SBO:0000290" size="1.4994" spatialDimensions="3" units="volume">
233 <notes>
234 <body xmlns="http://www.w3.org/1999/xhtml">
235 <p>Volume of the arterial blood. Note that this value is modified by allometric scaling in an initial
236 assignment or rule equation.</p>
237 </body>
238
239 </notes>
240 <annotation>
241 </annotation>
242 </compartment>
243 <compartment compartmentType="ORGAN" constant="true" id="VGut" metaid="_Sluka0002" name="VGut" sboTerm="SBO:0000290" size="1.1046" spatialDimensions="3" units="volume">
244 <notes>
245 <body xmlns="http://www.w3.org/1999/xhtml">
246 <p>Perfusable volume of the Gut (small intestine).
247 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
248 </body>
249
250 </notes>
251 <annotation>
252 </annotation>
253 </compartment>
254 <compartment compartmentType="LUMEN" constant="true" id="VGutLumen" metaid="_Sluka0003" name="VGutLumen" outside="VGut" sboTerm="SBO:0000290" size="1" spatialDimensions="3" units="volume">
255 <notes>
256 <body xmlns="http://www.w3.org/1999/xhtml">
257 <p>Lumen of the Gut. Note that the volume is arbitrary.</p>
258 </body>
259
260 </notes>
261 <annotation>
262 </annotation>
263 </compartment>
264 <compartment compartmentType="ORGAN" constant="true" id="VLung" metaid="_Sluka0004" name="VLung" sboTerm="SBO:0000290" size="0.5082" spatialDimensions="3" units="volume">
265 <notes>
266 <body xmlns="http://www.w3.org/1999/xhtml">
267 <p>Perfusable volume of the Lungs.
268 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
269 </body>
270
271 </notes>
272 <annotation>
273 </annotation>
274 </compartment>
275 <compartment compartmentType="CIRCULATORY" constant="true" id="VVen" metaid="_Sluka0005" name="VVen" sboTerm="SBO:0000290" size="3.4104" spatialDimensions="3" units="volume">
276 <notes>
277 <body xmlns="http://www.w3.org/1999/xhtml">
278 <p>Volume of the venous blood.
279 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
280 </body>
281
282 </notes>
283 <annotation>
284 </annotation>
285 </compartment>
286 <compartment compartmentType="ORGAN" constant="true" id="VRest" metaid="_Sluka0006" name="VRest" sboTerm="SBO:0000290" size="33.4698" spatialDimensions="3" units="volume">
287 <notes>
288 <body xmlns="http://www.w3.org/1999/xhtml">
289 <p>Perfusable volume of the Rest of the body, that is, all tissues and blood volumes not
290 explicitly described by other compartments.
291 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
292 </body>
293
294 </notes>
295 <annotation>
296 </annotation>
297 </compartment>
298 <compartment compartmentType="ORGAN" constant="true" id="VLiver" metaid="_Sluka0007" name="VLiver" sboTerm="SBO:0000290" size="1.7136" spatialDimensions="3" units="volume">
299 <notes>
300 <body xmlns="http://www.w3.org/1999/xhtml">
301 <p>Perfusable volume of the Liver.
302 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
303 </body>
304
305 </notes>
306 <annotation>
307 </annotation>
308 </compartment>
309 <compartment compartmentType="ORGAN" constant="true" id="VKidney" metaid="_Sluka0008" name="VKidney" sboTerm="SBO:0000290" size="0.294" spatialDimensions="3" units="volume">
310 <notes>
311 <body xmlns="http://www.w3.org/1999/xhtml">
312 <p>Perfusable volume of the Kidney.
313 The compartment volume is allometrically scaled and is assigned in an initialAssignment.</p>
314 </body>
315
316 </notes>
317 <annotation>
318 </annotation>
319 </compartment>
320 <compartment compartmentType="LUMEN" constant="true" id="VKidneyTubules" metaid="_Sluka0208" name="VKidneyTubules" outside="VKidney" sboTerm="SBO:0000290" size="1" spatialDimensions="3" units="volume">
321 <notes>
322 <body xmlns="http://www.w3.org/1999/xhtml">
323 <p>Kidney (renal) Tubules (lumen). This, like the gut lumen, is treated as a volumeless compartment.</p>
324 </body>
325
326 </notes>
327 <annotation>
328 </annotation>
329 </compartment>
330 </listOfCompartments>
331 <listOfSpecies>
332 <species boundaryCondition="false" compartment="VArt" constant="false" hasOnlySubstanceUnits="true" id="CArt" initialAmount="0" metaid="_Sluka0009" name="CArt" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
333 <notes>
334 <body xmlns="http://www.w3.org/1999/xhtml">
335 <p>Amount of APAP in the arteries of the gut in moles.</p>
336 </body>
337
338 </notes>
339 <annotation>
340 </annotation>
341 </species>
342 <species boundaryCondition="false" compartment="VGut" constant="false" hasOnlySubstanceUnits="true" id="CGut" initialAmount="0" metaid="_Sluka0010" name="CGut" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
343 <notes>
344 <body xmlns="http://www.w3.org/1999/xhtml">
345 <p>Amount of APAP in the gut (small intestine) blood in moles.</p>
346 </body>
347
348 </notes>
349 <annotation>
350 </annotation>
351 </species>
352 <species boundaryCondition="false" compartment="VGutLumen" constant="false" hasOnlySubstanceUnits="true" id="AGutlumen" initialAmount="0.0093" metaid="_Sluka0011" name="AGutlumen" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
353 <notes>
354 <body xmlns="http://www.w3.org/1999/xhtml">
355 <p>Amount of APAP in the lumen of the gut in moles.</p>
356 </body>
357
358 </notes>
359 <annotation>
360 </annotation>
361 </species>
362 <species boundaryCondition="false" compartment="VLung" constant="false" hasOnlySubstanceUnits="true" id="CLung" initialAmount="0" metaid="_Sluka0012" name="CLung" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
363 <notes>
364 <body xmlns="http://www.w3.org/1999/xhtml">
365 <p>Amount of APAP in the lung blood in moles.</p>
366 </body>
367
368 </notes>
369 <annotation>
370 </annotation>
371 </species>
372 <species boundaryCondition="false" compartment="VVen" constant="false" hasOnlySubstanceUnits="true" id="CVen" initialAmount="0" metaid="_Sluka0013" name="CVen" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
373 <notes>
374 <body xmlns="http://www.w3.org/1999/xhtml">
375 <p>Amount of APAP in the venous blood in moles.</p>
376 </body>
377
378 </notes>
379 <annotation>
380 </annotation>
381 </species>
382 <species boundaryCondition="false" compartment="VRest" constant="false" hasOnlySubstanceUnits="true" id="CRest" initialAmount="0" metaid="_Sluka0014" name="CRest" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
383 <notes>
384 <body xmlns="http://www.w3.org/1999/xhtml">
385 <p>Amount of APAP in the "rest of the body" in moles.</p>
386 </body>
387
388 </notes>
389 <annotation>
390 </annotation>
391 </species>
392 <species boundaryCondition="false" compartment="VLiver" constant="false" hasOnlySubstanceUnits="true" id="CLiver" initialAmount="0" metaid="_Sluka0015" name="CLiver" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
393 <notes>
394 <body xmlns="http://www.w3.org/1999/xhtml">
395 <p>Amount of APAP in the liver blood in moles.</p>
396 </body>
397
398 </notes>
399 <annotation>
400 </annotation>
401 </species>
402 <species boundaryCondition="false" compartment="VLiver" constant="false" hasOnlySubstanceUnits="true" id="CMetabolized" initialAmount="0" metaid="_Sluka0016" name="CMetabolized" sboTerm="SBO:0000247" speciesType="METAB" substanceUnits="substance">
403 <annotation>
404 </annotation>
405 </species>
406 <species boundaryCondition="false" compartment="VKidney" constant="false" hasOnlySubstanceUnits="true" id="CKidney" initialAmount="0" metaid="_Sluka0017" name="CKidney" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
407 <notes>
408 <body xmlns="http://www.w3.org/1999/xhtml">
409 <p>Amount of APAP in the kidney blood in moles.</p>
410 </body>
411
412 </notes>
413 <annotation>
414 </annotation>
415 </species>
416 <species boundaryCondition="false" compartment="VKidneyTubules" constant="false" hasOnlySubstanceUnits="true" id="CTubules" initialAmount="0" metaid="_Sluka0018" name="CTubules" sboTerm="SBO:0000247" speciesType="APAP" substanceUnits="substance">
417 <notes>
418 <body xmlns="http://www.w3.org/1999/xhtml">
419 <p>Amount of APAP in the Kidney Tubules in moles.</p>
420 </body>
421
422 </notes>
423 <annotation>
424 </annotation>
425 </species>
426 </listOfSpecies>
427 <listOfParameters>
428 <parameter constant="true" id="APAP_Dose_grams" metaid="_4d72c947-dc0d-4557-ab4f-542a7d0745d9" name="APAP_Dose_grams" sboTerm="SBO:0000504" units="gram" value="1.4">
429 <notes>
430 <body xmlns="http://www.w3.org/1999/xhtml">
431 <p>APAP dose in grams.</p>
432 </body>
433
434 </notes>
435 </parameter>
436 <parameter constant="true" id="APAP_MW" metaid="_Sluka0039" name="APAP_MW" sboTerm="SBO:0000002" units="grams2mol" value="151.2">
437 <notes>
438 <body xmlns="http://www.w3.org/1999/xhtml">
439 <p>Acetaminophen molecular weight in grams/mole.</p>
440 </body>
441
442 </notes>
443 </parameter>
444 <parameter constant="true" id="APAP_Dose" metaid="_Sluka0040" name="APAP_Dose" sboTerm="SBO:0000002" units="substance" value="1">
445 <notes>
446 <body xmlns="http://www.w3.org/1999/xhtml">
447 <p>Acetaminophen dose in moles. = APAP_Dose_grams/APAP_MW. Note that this value is assigned by an initial assignment or rule equation.</p>
448 </body>
449
450 </notes>
451 </parameter>
452 <parameter constant="true" id="BW" metaid="_Sluka0041" name="BW" sboTerm="SBO:0000002" units="kilogram" value="70">
453 <notes>
454 <body xmlns="http://www.w3.org/1999/xhtml">
455 <p>Body weight, in Kg. This value, raised to the 3/4 power, is used in the allometric scaling equations</p>
456 </body>
457
458 </notes>
459 <annotation>
460 </annotation>
461 </parameter>
462 <parameter constant="true" id="BW_ref" metaid="_0e4ee21f-de1b-45f5-bf7b-cd4bf122ecd3" name="BW_ref" sboTerm="SBO:0000381" units="BW_ref" value="1">
463 <notes>
464 <body xmlns="http://www.w3.org/1999/xhtml">
465 <p>De-dimensionalization factor for the allometric scaling. Removes the non-integer exponent of the BW^(3/4) scaling factor in the allometric equations.</p>
466 </body>
467
468 </notes>
469 </parameter>
470 <parameter constant="true" id="Cardiac_flow_ref" metaid="c99b2944-033f-4160-96f8-2ddaad309c4a" name="Cardiac_flow_ref" sboTerm="SBO:0000380" units="Volumetric_Flow" value="15">
471 <notes>
472 <body xmlns="http://www.w3.org/1999/xhtml">
473 <p>Total cardiac output reference value for individual of BW=BW_ref (70Kg) for allometric scaling. In Litres/hour.</p>
474 </body>
475
476 </notes>
477 </parameter>
478 <parameter constant="false" id="QCardiac" metaid="_Sluka0022" name="QCardiac" sboTerm="SBO:0000016" units="Volumetric_Flow" value="363">
479 <notes>
480 <body xmlns="http://www.w3.org/1999/xhtml">
481 <p>Cardiac blood flow in Litres/hr. (aka arterial blood flow or QArt).
482 Note that this value is modified by allometric scaling in an
483 initial assignment or rule equation.</p>
484 </body>
485
486 </notes>
487 <annotation>
488 </annotation>
489 </parameter>
490 <parameter id="QGut_fraction_QCardiac" metaid="_6fe578ca-faa4-496a-9c77-7848792830c8" name="QGut_fraction_QCardiac" sboTerm="SBO:0000380" units="dimensionless" value="0.205">
491 <notes>
492 <body xmlns="http://www.w3.org/1999/xhtml">
493 <p>Allometric scaling coefficient for fraction of cardiac output (QCardiac) that flows through the Gut (QGut).</p>
494 </body>
495
496 </notes>
497 </parameter>
498 <parameter constant="false" id="QGut" metaid="_Sluka0019" name="QGut" sboTerm="SBO:0000016" units="Volumetric_Flow" value="74.42">
499 <notes>
500 <body xmlns="http://www.w3.org/1999/xhtml">
501 <p>Volumetric blood flow through the gut in Litres/hour. Note that this value is modified by allometric scaling in
502 an initial assignment or rule equation.</p>
503 </body>
504
505 </notes>
506 </parameter>
507 <parameter id="QLiver_fraction_QCardiac" metaid="_9a2d20d3-2d96-4720-a7bd-fb3570d7d57e" name="QLiver_fraction_QCardiac" sboTerm="SBO:0000380" units="dimensionless" value="0.0535">
508 <notes>
509 <body xmlns="http://www.w3.org/1999/xhtml">
510 <p>Allometric scaling coefficient for fraction of cardiac output (QCardiac) that flows through the Liver (QLiver).</p>
511 </body>
512
513 </notes>
514 </parameter>
515 <parameter constant="false" id="QLiver" metaid="_Sluka0030" name="QLiver" sboTerm="SBO:0000016" units="Volumetric_Flow" value="19.42">
516 <notes>
517 <body xmlns="http://www.w3.org/1999/xhtml">
518 <p>Perfusable volume of the Liver in Litres/hr. Note that this value is modified by allometric scaling in an initial
519 assignment or rule equation.</p>
520 </body>
521
522 </notes>
523 </parameter>
524 <parameter id="QKidney_fraction_QCardiac" metaid="_2f0d6351-6a9e-4dc2-b1e7-e2cf830dea70" name="QKidney_fraction_QCardiac" sboTerm="SBO:0000380" units="dimensionless" value="0.2214">
525 <notes>
526 <body xmlns="http://www.w3.org/1999/xhtml">
527 <p>Allometric scaling coefficient for fraction of cardiac output (QCardiac) that flows through the Kidney (QKidney).</p>
528 </body>
529
530 </notes>
531 </parameter>
532 <parameter constant="false" id="QKidney" metaid="_Sluka0035" name="QKidney" sboTerm="SBO:0000016" units="Volumetric_Flow" value="80.37">
533 <notes>
534 <body xmlns="http://www.w3.org/1999/xhtml">
535 <p>Kidney blood flow in Litres/hr. Note that this value is modified by allometric scaling
536 in an initial assignment or rule equation.</p>
537 </body>
538
539 </notes>
540 </parameter>
541 <parameter constant="false" id="QRest" metaid="_Sluka0025" name="QRest" sboTerm="SBO:0000016" units="Volumetric_Flow" value="188.8">
542 <notes>
543 <body xmlns="http://www.w3.org/1999/xhtml">
544 <p>Blood throw through all other tissues, Litres/hour. Note that this value is modified by allometric scaling in an
545 initial assignment or rule equation.</p>
546 </body>
547
548 </notes>
549 </parameter>
550 <parameter constant="true" id="QGFR_ref" metaid="d2e1b1e1-958e-46da-9fd8-861e53cb67fd" name="QGFR_ref" sboTerm="SBO:0000380" units="Volumetric_Flow" value="0.039">
551 <notes>
552 <body xmlns="http://www.w3.org/1999/xhtml">
553 <p>Qgfr coefficient for allometric scaling.</p>
554 <p> <b>NOTE:
555 The normal value for this parameter is 21.7L/hr.</b>
556 The value shown here reflects the extensive re-adsorption of APAP from the kidney tubules back into the blood.</p>
557 </body>
558
559 </notes>
560 </parameter>
561 <parameter constant="false" id="Qgfr" metaid="_Sluka0036" name="Qgfr" sboTerm="SBO:0000016" units="Volumetric_Flow" value="0.9438">
562 <notes>
563 <body xmlns="http://www.w3.org/1999/xhtml">
564 <p>Granulocyte filtration rate in Litres/hour. Note that this value is modified by allometric scaling in
565 an initial assignment or rule equation. In addition, this vlue is greatly reduced to simulate resorption of APAP from the tubules in the kidney.</p>
566 </body>
567
568 </notes>
569 <annotation>
570 </annotation>
571 </parameter>
572 <parameter constant="true" id="kGutabs" metaid="_Sluka0021" name="kGutabs" sboTerm="SBO:0000016" units="first_order_rate_constant" value="1.5"/>
573 <parameter constant="true" id="CLmetabolism" metaid="_Sluka0031" name="CLmetabolism" sboTerm="SBO:0000016" units="first_order_rate_constant" value="9.5">
574 <notes>
575 <body xmlns="http://www.w3.org/1999/xhtml">
576 <p>Rate of metabolism of APAP in the liver. This single kinetic constant represents both Phase I (e.g., Cyp-2E1) and Phase II (glucurondiation and sulfation) metabolism.</p>
577 </body>
578
579 </notes>
580 <annotation>
581 </annotation>
582 </parameter>
583 <parameter constant="true" id="Fraction_unbound_plasma" metaid="_Sluka0028" name="Fraction_unbound_plasma" sboTerm="SBO:0000470" units="dimensionless" value="0.8">
584 <notes>
585 <body xmlns="http://www.w3.org/1999/xhtml">
586 <p>Fraction of compound in plasma that is not bound by plasma proteins.</p>
587 </body>
588
589 </notes>
590 </parameter>
591 <parameter constant="true" id="Ratioblood2plasma" metaid="_Sluka0026" name="Ratioblood2plasma" sboTerm="SBO:0000470" units="dimensionless" value="1.09">
592 <notes>
593 <body xmlns="http://www.w3.org/1999/xhtml">
594 <p>Ratio of the compound amount in (total) blood vs. plasma.</p>
595 </body>
596
597 </notes>
598 </parameter>
599 <parameter constant="true" id="Kliver2plasma" metaid="_Sluka0032" name="Kliver2plasma" sboTerm="SBO:0000281" units="dimensionless" value="1">
600 <notes>
601 <body xmlns="http://www.w3.org/1999/xhtml">
602 <p>Partition coefficient for compound between the Liver and the blood plasma.</p>
603 </body>
604
605 </notes>
606 </parameter>
607 <parameter constant="true" id="Kkidney2plasma" metaid="_Sluka0037" name="Kkidney2plasma" sboTerm="SBO:0000281" units="dimensionless" value="1">
608 <notes>
609 <body xmlns="http://www.w3.org/1999/xhtml">
610 <p>Partition coefficient for compound between the Kidney and the blood plasma.</p>
611 </body>
612
613 </notes>
614 </parameter>
615 <parameter constant="true" id="KRest2plasma" metaid="_Sluka0027" name="KRest2plasma" sboTerm="SBO:0000281" units="dimensionless" value="1.6">
616 <notes>
617 <body xmlns="http://www.w3.org/1999/xhtml">
618 <p>Partition coefficient for compound between the Rest (of body) and the blood plasma.</p>
619 </body>
620
621 </notes>
622 </parameter>
623 <parameter constant="true" id="VTotal_ref" metaid="_87a706ef-f1ea-4eb5-bd5a-0b8825495dd6" name="VTotal_ref" sboTerm="SBO:0000380" units="volume" value="0.6">
624 <notes>
625 <body xmlns="http://www.w3.org/1999/xhtml">
626 <p>Total perfusable volume of the body coefficient for allometric scaling. This is the lean fraction of Body Weight.</p>
627 </body>
628
629 </notes>
630 </parameter>
631 <parameter constant="false" id="VTotal" metaid="_Sluka0042" name="VTotal" sboTerm="SBO:0000468" units="volume" value="42">
632 <notes>
633 <body xmlns="http://www.w3.org/1999/xhtml">
634 <p>Total perfusable volume of the body in Litres. Note that this value is modified by allometric scaling in an initial assignment or rule equation.</p>
635 </body>
636
637 </notes>
638 </parameter>
639 <parameter id="VLiver_fraction_VTotal" metaid="_5283340a-3f7d-40b9-adc9-788546db0cac" name="VLiver_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.0408">
640 <notes>
641 <body xmlns="http://www.w3.org/1999/xhtml">
642 <p>Allometric scaling coefficient for fraction of total perfusable volume of the body (VTotal) represented by the Liver (VLiver).</p>
643 </body>
644
645 </notes>
646 </parameter>
647 <parameter id="VArt_fraction_VTotal" metaid="b56c2f24-4e12-4944-b768-9552d15b8bf6" name="VArt_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.0357">
648 <notes>
649 <body xmlns="http://www.w3.org/1999/xhtml">
650 <p>Allometric scaling coefficient for fraction of cardiac output (QCardiac) that flows through the Arteries (QArt).</p>
651 </body>
652
653 </notes>
654 </parameter>
655 <parameter id="VLung_fraction_VTotal" metaid="acb9c91f-7518-44a1-9555-f72c89184d29" name="VLung_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.0121">
656 <notes>
657 <body xmlns="http://www.w3.org/1999/xhtml">
658 <p>Allometric scaling coefficient for fraction of total perfusable volume of the body (VTotal) represented by the Lungs (VLung).</p>
659 </body>
660
661 </notes>
662 </parameter>
663 <parameter id="VVen_fraction_VTotal" metaid="_4f8549f7-1d1d-4047-91c2-6e3ce324576d" name="VVen_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.0812">
664 <notes>
665 <body xmlns="http://www.w3.org/1999/xhtml">
666 <p>Allometric scaling coefficient for fraction of total perfusable volume of the body (VTotal) represented by the Veins (VVen).</p>
667 </body>
668
669 </notes>
670 </parameter>
671 <parameter id="VGut_fraction_VTotal" metaid="a2571ef7-3a0c-413c-a255-9b252ddd0f3d" name="VGut_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.0263">
672 <notes>
673 <body xmlns="http://www.w3.org/1999/xhtml">
674 <p>Allometric scaling coefficient for fraction of total perfusable volume of the body (VTotal) represented by the Gut/stomach/small intestine (VGut).</p>
675 </body>
676
677 </notes>
678 </parameter>
679 <parameter id="VKidney_fraction_VTotal" metaid="adaf453a-6416-4241-b2de-73f2e1ee71fc" name="VKidney_fraction_VTotal" sboTerm="SBO:0000380" units="dimensionless" value="0.007">
680 <notes>
681 <body xmlns="http://www.w3.org/1999/xhtml">
682 <p>Allometric scaling coefficient for fraction of total perfusable volume of the body (VTotal) represented by the Kidneys (VKidney).</p>
683 </body>
684
685 </notes>
686 </parameter>
687 </listOfParameters>
688 <listOfInitialAssignments>
689 <initialAssignment metaid="_2dca2124-6aac-4a9b-b2fa-8f1a232e7427" sboTerm="SBO:0000064" symbol="VArt">
690 <notes>
691 <body xmlns="http://www.w3.org/1999/xhtml">
692 <p>Assignment of the perfusable volume (L) of the Arterial (Art) compartment after allometric scaling.</p>
693 </body>
694
695 </notes>
696 <math xmlns="http://www.w3.org/1998/Math/MathML">
697 <apply>
698 <times/>
699 <ci> VTotal </ci>
700 <ci> VArt_fraction_VTotal </ci>
701 </apply>
702 </math>
703 </initialAssignment>
704 <initialAssignment metaid="f9cc931e-3865-410e-b3d1-e83fa81d43f8" sboTerm="SBO:0000064" symbol="VGut">
705 <notes>
706 <body xmlns="http://www.w3.org/1999/xhtml">
707 <p>Assignment of the perfusable volume (L) of the Gut compartment after allometric scaling.</p>
708 </body>
709
710 </notes>
711 <math xmlns="http://www.w3.org/1998/Math/MathML">
712 <apply>
713 <times/>
714 <ci> VTotal </ci>
715 <ci> VGut_fraction_VTotal </ci>
716 </apply>
717 </math>
718 </initialAssignment>
719 <initialAssignment metaid="cf2ac2fa-881d-4dc4-bc96-58f52d3ebdd8" sboTerm="SBO:0000064" symbol="VLung">
720 <notes>
721 <body xmlns="http://www.w3.org/1999/xhtml">
722 <p>Assignment of the perfusable volume (L) of the Lung compartment after allometric scaling.</p>
723 </body>
724
725 </notes>
726 <math xmlns="http://www.w3.org/1998/Math/MathML">
727 <apply>
728 <times/>
729 <ci> VTotal </ci>
730 <ci> VLung_fraction_VTotal </ci>
731 </apply>
732 </math>
733 </initialAssignment>
734 <initialAssignment metaid="_62994f33-ccb7-422c-b3be-676ed3a09ec3" sboTerm="SBO:0000064" symbol="VVen">
735 <notes>
736 <body xmlns="http://www.w3.org/1999/xhtml">
737 <p>Assignment of the perfusable volume (L) of the Venous (Ven) compartment after allometric scaling.</p>
738 </body>
739
740 </notes>
741 <math xmlns="http://www.w3.org/1998/Math/MathML">
742 <apply>
743 <times/>
744 <ci> VTotal </ci>
745 <ci> VVen_fraction_VTotal </ci>
746 </apply>
747 </math>
748 </initialAssignment>
749 <initialAssignment metaid="de5ea7ea-1072-48e3-aae4-66b2b0fd5f34" sboTerm="SBO:0000064" symbol="VLiver">
750 <notes>
751 <body xmlns="http://www.w3.org/1999/xhtml">
752 <p>Assignment of the perfusable volume (L) of the Liver compartment after allometric scaling.</p>
753 </body>
754
755 </notes>
756 <math xmlns="http://www.w3.org/1998/Math/MathML">
757 <apply>
758 <times/>
759 <ci> VTotal </ci>
760 <ci> VLiver_fraction_VTotal </ci>
761 </apply>
762 </math>
763 </initialAssignment>
764 <initialAssignment metaid="_8f27004d-54d1-4e4a-9349-898fd8938629" sboTerm="SBO:0000064" symbol="VKidney">
765 <notes>
766 <body xmlns="http://www.w3.org/1999/xhtml">
767 <p>Assignment of the perfusable volume (L) of the Kidney compartment after allometric scaling.</p>
768 </body>
769
770 </notes>
771 <math xmlns="http://www.w3.org/1998/Math/MathML">
772 <apply>
773 <times/>
774 <ci> VTotal </ci>
775 <ci> VKidney_fraction_VTotal </ci>
776 </apply>
777 </math>
778 </initialAssignment>
779 <initialAssignment metaid="_8d0e0a37-a0ad-4467-b456-39bfd8377d3f" sboTerm="SBO:0000064" symbol="VRest">
780 <notes>
781 <body xmlns="http://www.w3.org/1999/xhtml">
782 <p>Assignment of the perfusable volume (L) of the Rest (of the body) compartment after allometric scaling.</p>
783 </body>
784
785 </notes>
786 <math xmlns="http://www.w3.org/1998/Math/MathML">
787 <apply>
788 <minus/>
789 <apply>
790 <minus/>
791 <apply>
792 <minus/>
793 <apply>
794 <minus/>
795 <apply>
796 <minus/>
797 <apply>
798 <minus/>
799 <ci> VTotal </ci>
800 <ci> VArt </ci>
801 </apply>
802 <ci> VGut </ci>
803 </apply>
804 <ci> VKidney </ci>
805 </apply>
806 <ci> VLiver </ci>
807 </apply>
808 <ci> VLung </ci>
809 </apply>
810 <ci> VVen </ci>
811 </apply>
812 </math>
813 </initialAssignment>
814 <initialAssignment metaid="_0c460a20-17e9-474c-bb45-ce5fea278500" sboTerm="SBO:0000064" symbol="APAP_Dose">
815 <notes>
816 <body xmlns="http://www.w3.org/1999/xhtml">
817 <p>Calculate APAP dose in moles based on the dose in grams (APAP_Dose_grams) and APAP moleuclar weight (APAP_MW).</p>
818 </body>
819
820 </notes>
821 <math xmlns="http://www.w3.org/1998/Math/MathML">
822 <apply>
823 <divide/>
824 <ci> APAP_Dose_grams </ci>
825 <ci> APAP_MW </ci>
826 </apply>
827 </math>
828 </initialAssignment>
829 <initialAssignment metaid="dcbfae70-b16b-4ff0-b2b3-6f4a8a5021bb" sboTerm="SBO:0000064" symbol="AGutlumen">
830 <notes>
831 <body xmlns="http://www.w3.org/1999/xhtml">
832 <p>Starting compartment for the APAP dose (moles) is the lumen of the gut/stomach/small intestine.</p>
833 </body>
834
835 </notes>
836 <math xmlns="http://www.w3.org/1998/Math/MathML">
837 <ci> APAP_Dose </ci>
838 </math>
839 </initialAssignment>
840 <initialAssignment metaid="_38732f83-f67b-47ac-9b44-4766dee8d5ed" sboTerm="SBO:0000064" symbol="QCardiac">
841 <notes>
842 <body xmlns="http://www.w3.org/1999/xhtml">
843 <p>Allometric calculation of the total cardiac output inL/hour (QCardiac) based on the body weight ( (BW/BW_ref)^(3/4) ).</p>
844 </body>
845
846 </notes>
847 <math xmlns="http://www.w3.org/1998/Math/MathML">
848 <apply>
849 <times/>
850 <ci> Cardiac_flow_ref </ci>
851 <apply>
852 <power/>
853 <apply>
854 <divide/>
855 <ci> BW </ci>
856 <ci> BW_ref </ci>
857 </apply>
858 <cn> 0.75 </cn>
859 </apply>
860 </apply>
861 </math>
862 </initialAssignment>
863 <initialAssignment metaid="_8ea66927-800e-4e37-9295-4081c15cba6b" sboTerm="SBO:0000064" symbol="QGut">
864 <notes>
865 <body xmlns="http://www.w3.org/1999/xhtml">
866 <p>Allometric calculation of the Gut blood flow rate (QGut) in L/hour based on the body weight ( BW^(3/4) ).</p>
867 </body>
868
869 </notes>
870 <math xmlns="http://www.w3.org/1998/Math/MathML">
871 <apply>
872 <times/>
873 <ci> QCardiac </ci>
874 <ci> QGut_fraction_QCardiac </ci>
875 </apply>
876 </math>
877 </initialAssignment>
878 <initialAssignment metaid="_995ad95b-8c26-4287-930f-009230fb8fff" sboTerm="SBO:0000064" symbol="QLiver">
879 <notes>
880 <body xmlns="http://www.w3.org/1999/xhtml">
881 <p>Allometric calculation of the Liver blood flow rate (QLiver) in L/hour based on the body weight ( BW^(3/4) ).</p>
882 </body>
883
884 </notes>
885 <math xmlns="http://www.w3.org/1998/Math/MathML">
886 <apply>
887 <times/>
888 <ci> QCardiac </ci>
889 <ci> QLiver_fraction_QCardiac </ci>
890 </apply>
891 </math>
892 </initialAssignment>
893 <initialAssignment metaid="d4eb1ec0-c1c6-47ab-9219-f443a96a84ae" sboTerm="SBO:0000064" symbol="QKidney">
894 <notes>
895 <body xmlns="http://www.w3.org/1999/xhtml">
896 <p>Allometric calculation of the Kidney blood flow rate (QKidney) in L/hour based on the body weight ( BW^(3/4) ).</p>
897 </body>
898
899 </notes>
900 <math xmlns="http://www.w3.org/1998/Math/MathML">
901 <apply>
902 <times/>
903 <ci> QCardiac </ci>
904 <ci> QKidney_fraction_QCardiac </ci>
905 </apply>
906 </math>
907 </initialAssignment>
908 <initialAssignment metaid="d0fa26d6-0baa-41fc-906b-bd969fa00c69" sboTerm="SBO:0000064" symbol="QRest">
909 <notes>
910 <body xmlns="http://www.w3.org/1999/xhtml">
911 <p>Allometric calculation of the Rest of the body's blood flow rate (QRest) in L/hour based on the body weight ( BW^(3/4) ).</p>
912 </body>
913
914 </notes>
915 <math xmlns="http://www.w3.org/1998/Math/MathML">
916 <apply>
917 <minus/>
918 <apply>
919 <minus/>
920 <apply>
921 <minus/>
922 <ci> QCardiac </ci>
923 <ci> QGut </ci>
924 </apply>
925 <ci> QKidney </ci>
926 </apply>
927 <ci> QLiver </ci>
928 </apply>
929 </math>
930 </initialAssignment>
931 <initialAssignment metaid="cac0ce12-7358-4bee-a30c-547c5720eaff" sboTerm="SBO:0000064" symbol="Qgfr">
932 <notes>
933 <body xmlns="http://www.w3.org/1999/xhtml">
934 <p>Allometric calculation of the Qgfr inL/hour based on the body weight ( (BW/BW_ref)^(3/4) ).</p>
935 </body>
936
937 </notes>
938 <math xmlns="http://www.w3.org/1998/Math/MathML">
939 <apply>
940 <times/>
941 <ci> QGFR_ref </ci>
942 <apply>
943 <power/>
944 <apply>
945 <divide/>
946 <ci> BW </ci>
947 <ci> BW_ref </ci>
948 </apply>
949 <cn> 0.75 </cn>
950 </apply>
951 </apply>
952 </math>
953 </initialAssignment>
954 <initialAssignment metaid="e1195787-cc6f-4a24-8b19-85cad5a988f3" sboTerm="SBO:0000064" symbol="VTotal">
955 <notes>
956 <body xmlns="http://www.w3.org/1999/xhtml">
957 <p>Allometric calculation of the total perfusable volume of the body in litres (VTotal) based on the body weight.</p>
958 </body>
959
960 </notes>
961 <math xmlns="http://www.w3.org/1998/Math/MathML">
962 <apply>
963 <times/>
964 <ci> VTotal_ref </ci>
965 <apply>
966 <divide/>
967 <ci> BW </ci>
968 <ci> BW_ref </ci>
969 </apply>
970 </apply>
971 </math>
972 </initialAssignment>
973 </listOfInitialAssignments>
974 <listOfReactions>
975 <reaction id="J1" metaid="_Sluka0043" name="J01" reversible="false" sboTerm="SBO:0000185">
976 <notes>
977 <body xmlns="http://www.w3.org/1999/xhtml">
978 <p>Blood born transfer of compound from the Arterial compartment (CArt) to the Gut (CGut) in moles/hour.</p>
979 </body>
980
981 </notes>
982 <listOfReactants>
983 <speciesReference metaid="a8633208-82fc-4d23-94b5-2bc5245ee07e" species="CArt" stoichiometry="1"/>
984 </listOfReactants>
985 <listOfProducts>
986 <speciesReference metaid="_5223c5d3-3eff-4ba8-811a-1b6e14bf57f4" species="CGut" stoichiometry="1"/>
987 </listOfProducts>
988 <kineticLaw metaid="_5ade5390-e618-4663-b1a0-9c3bf7b09927">
989 <math xmlns="http://www.w3.org/1998/Math/MathML">
990 <apply>
991 <times/>
992 <apply>
993 <divide/>
994 <ci> QGut </ci>
995 <ci> VArt </ci>
996 </apply>
997 <ci> CArt </ci>
998 </apply>
999 </math>
1000 </kineticLaw>
1001 </reaction>
1002 <reaction id="J2" metaid="_Sluka0044" name="J02" reversible="false" sboTerm="SBO:0000185">
1003 <notes>
1004 <body xmlns="http://www.w3.org/1999/xhtml">
1005 <p>First order adsorption of compound from the lumen of the gut (AGutlumen) to the gut compartment (CGut) in mole/hour.</p>
1006 </body>
1007
1008 </notes>
1009 <listOfReactants>
1010 <speciesReference metaid="_7026dbef-590b-4750-80f2-85f015556633" species="AGutlumen" stoichiometry="1"/>
1011 </listOfReactants>
1012 <listOfProducts>
1013 <speciesReference metaid="f166049b-8cb8-4b02-bf63-7e3ad43ed420" species="CGut" stoichiometry="1"/>
1014 </listOfProducts>
1015 <kineticLaw metaid="c5889f07-c411-4d95-bd03-1a4d8c308a61">
1016 <math xmlns="http://www.w3.org/1998/Math/MathML">
1017 <apply>
1018 <times/>
1019 <ci> kGutabs </ci>
1020 <ci> AGutlumen </ci>
1021 </apply>
1022 </math>
1023 </kineticLaw>
1024 </reaction>
1025 <reaction id="J3" metaid="_Sluka0045" name="J03" reversible="false" sboTerm="SBO:0000185">
1026 <notes>
1027 <body xmlns="http://www.w3.org/1999/xhtml">
1028 <p>Blood born transfer of compound from the Lung compartment (CLung) to the Arterial blood compartment (CArt) in moles/hour.</p>
1029 </body>
1030
1031 </notes>
1032 <listOfReactants>
1033 <speciesReference metaid="_54a2ca4b-8777-4b4e-915f-06ed04377a17" species="CLung" stoichiometry="1"/>
1034 </listOfReactants>
1035 <listOfProducts>
1036 <speciesReference metaid="_46332a91-6207-4125-9a6d-9e49be0a4630" species="CArt" stoichiometry="1"/>
1037 </listOfProducts>
1038 <kineticLaw metaid="_1b1d05bb-d21a-4748-958a-7d3f2d9e1d52">
1039 <math xmlns="http://www.w3.org/1998/Math/MathML">
1040 <apply>
1041 <times/>
1042 <apply>
1043 <divide/>
1044 <ci> QCardiac </ci>
1045 <ci> VLung </ci>
1046 </apply>
1047 <ci> CLung </ci>
1048 </apply>
1049 </math>
1050 </kineticLaw>
1051 </reaction>
1052 <reaction id="J4" metaid="_Sluka0046" name="J04" reversible="false" sboTerm="SBO:0000185">
1053 <notes>
1054 <body xmlns="http://www.w3.org/1999/xhtml">
1055 <p>Blood born transfer of compound from the Venous compartment (CVen) to the Lung compartment (CLung) in moles/hour.</p>
1056 </body>
1057
1058 </notes>
1059 <listOfReactants>
1060 <speciesReference metaid="f6436b54-997c-4aa2-b447-3cc50a47d867" species="CVen" stoichiometry="1"/>
1061 </listOfReactants>
1062 <listOfProducts>
1063 <speciesReference metaid="c2fbf57d-052e-4a74-80ab-06e20335403c" species="CLung" stoichiometry="1"/>
1064 </listOfProducts>
1065 <kineticLaw metaid="b21496a9-5dae-4ac7-9bae-84570bac9215">
1066 <math xmlns="http://www.w3.org/1998/Math/MathML">
1067 <apply>
1068 <times/>
1069 <apply>
1070 <divide/>
1071 <ci> QCardiac </ci>
1072 <ci> VVen </ci>
1073 </apply>
1074 <ci> CVen </ci>
1075 </apply>
1076 </math>
1077 </kineticLaw>
1078 </reaction>
1079 <reaction id="J5" metaid="_Sluka0047" name="J05" reversible="false" sboTerm="SBO:0000185">
1080 <notes>
1081 <body xmlns="http://www.w3.org/1999/xhtml">
1082 <p>Blood born transfer of compound from the Arterial compartment (CArt) to the Rest of the body compartment (CRest) in moles/hour.</p>
1083 </body>
1084
1085 </notes>
1086 <listOfReactants>
1087 <speciesReference metaid="e87e80e4-0001-42c3-add8-813aed5ea769" species="CArt" stoichiometry="1"/>
1088 </listOfReactants>
1089 <listOfProducts>
1090 <speciesReference metaid="_5f0d33f7-f647-4e99-a392-5b0ba3bd7ec8" species="CRest" stoichiometry="1"/>
1091 </listOfProducts>
1092 <kineticLaw metaid="_5ac5b372-7927-4b17-9659-5797277fe475">
1093 <math xmlns="http://www.w3.org/1998/Math/MathML">
1094 <apply>
1095 <times/>
1096 <ci> QRest </ci>
1097 <apply>
1098 <divide/>
1099 <ci> CArt </ci>
1100 <ci> VArt </ci>
1101 </apply>
1102 </apply>
1103 </math>
1104 </kineticLaw>
1105 </reaction>
1106 <reaction id="J6" metaid="_Sluka0048" name="J06" reversible="false" sboTerm="SBO:0000185">
1107 <notes>
1108 <body xmlns="http://www.w3.org/1999/xhtml">
1109 <p>Blood born transfer of compound from the Rest compartment (CRest) to the Venous compartment (CVen) in moles/hour.</p>
1110 </body>
1111
1112 </notes>
1113 <listOfReactants>
1114 <speciesReference metaid="acb6b858-561a-4175-9125-2acfe8a50286" species="CRest" stoichiometry="1"/>
1115 </listOfReactants>
1116 <listOfProducts>
1117 <speciesReference metaid="_785d3f9d-4b81-4573-8b06-5d9306426232" species="CVen" stoichiometry="1"/>
1118 </listOfProducts>
1119 <kineticLaw metaid="fcdeaa05-38bc-4409-8f77-fbc4e6a9db4e">
1120 <math xmlns="http://www.w3.org/1998/Math/MathML">
1121 <apply>
1122 <divide/>
1123 <apply>
1124 <times/>
1125 <apply>
1126 <times/>
1127 <apply>
1128 <divide/>
1129 <ci> QRest </ci>
1130 <ci> VRest </ci>
1131 </apply>
1132 <ci> CRest </ci>
1133 </apply>
1134 <ci> Ratioblood2plasma </ci>
1135 </apply>
1136 <apply>
1137 <times/>
1138 <ci> KRest2plasma </ci>
1139 <ci> Fraction_unbound_plasma </ci>
1140 </apply>
1141 </apply>
1142 </math>
1143 </kineticLaw>
1144 </reaction>
1145 <reaction id="J7" metaid="_Sluka0049" name="J07" reversible="false" sboTerm="SBO:0000185">
1146 <notes>
1147 <body xmlns="http://www.w3.org/1999/xhtml">
1148 <p>Blood born transfer of compound from the Arterial compartment (CArt) to the Liver compartment (CLiver) in moles/hour.</p>
1149 </body>
1150
1151 </notes>
1152 <listOfReactants>
1153 <speciesReference metaid="_4b8efcf5-191f-4ee1-9ada-b932bd5ae2ea" species="CArt" stoichiometry="1"/>
1154 </listOfReactants>
1155 <listOfProducts>
1156 <speciesReference metaid="_26cfdf3d-7b1e-41fa-aa2f-111362e23447" species="CLiver" stoichiometry="1"/>
1157 </listOfProducts>
1158 <kineticLaw metaid="_0ee22f51-374e-4649-b197-b20fa9379e3e">
1159 <math xmlns="http://www.w3.org/1998/Math/MathML">
1160 <apply>
1161 <times/>
1162 <apply>
1163 <divide/>
1164 <ci> QLiver </ci>
1165 <ci> VArt </ci>
1166 </apply>
1167 <ci> CArt </ci>
1168 </apply>
1169 </math>
1170 </kineticLaw>
1171 </reaction>
1172 <reaction id="J8" metaid="_Sluka0050" name="J08" reversible="false" sboTerm="SBO:0000182">
1173 <notes>
1174 <body xmlns="http://www.w3.org/1999/xhtml">
1175 <p>Metabolism of compound in the Liver compartment (CLiver) to metabolites (CMetabolized) in moles/hour. The metabolites stay in the liver compartment. This single first order ODE represents both Phase I (Cyp-P450 2E1, 1A2) and Phase II (glucuronidation and sulfation) reactions.</p>
1176 </body>
1177
1178 </notes>
1179 <listOfReactants>
1180 <speciesReference metaid="_7f0fe6d4-0597-47f5-81a4-04135c3bc05d" species="CLiver" stoichiometry="1"/>
1181 </listOfReactants>
1182 <listOfProducts>
1183 <speciesReference metaid="_59dafa8e-58dc-4fed-907c-664f34165acd" species="CMetabolized" stoichiometry="1"/>
1184 </listOfProducts>
1185 <kineticLaw metaid="_443720c5-d93b-43b6-942d-f9f9554ad23c">
1186 <math xmlns="http://www.w3.org/1998/Math/MathML">
1187 <apply>
1188 <divide/>
1189 <apply>
1190 <times/>
1191 <ci> CLmetabolism </ci>
1192 <ci> CLiver </ci>
1193 </apply>
1194 <apply>
1195 <times/>
1196 <ci> Kliver2plasma </ci>
1197 <ci> Fraction_unbound_plasma </ci>
1198 </apply>
1199 </apply>
1200 </math>
1201 </kineticLaw>
1202 </reaction>
1203 <reaction id="J9" metaid="_Sluka0051" name="J09" reversible="false" sboTerm="SBO:0000185">
1204 <notes>
1205 <body xmlns="http://www.w3.org/1999/xhtml">
1206 <p>Blood born transfer of compound from the Gut compartment (CGut) to the Liver compartment (CLiver) in moles/hour.</p>
1207 </body>
1208
1209 </notes>
1210 <listOfReactants>
1211 <speciesReference metaid="f51a3c38-98d5-4fdd-bb06-68ffceab73bf" species="CGut" stoichiometry="1"/>
1212 </listOfReactants>
1213 <listOfProducts>
1214 <speciesReference metaid="_542c95ef-c35a-4db9-8fab-69c3cd9d6896" species="CLiver" stoichiometry="1"/>
1215 </listOfProducts>
1216 <kineticLaw metaid="b243af42-e239-4bb1-bb7e-2d6413c2cacf">
1217 <math xmlns="http://www.w3.org/1998/Math/MathML">
1218 <apply>
1219 <times/>
1220 <apply>
1221 <divide/>
1222 <ci> QGut </ci>
1223 <ci> VGut </ci>
1224 </apply>
1225 <ci> CGut </ci>
1226 </apply>
1227 </math>
1228 </kineticLaw>
1229 </reaction>
1230 <reaction id="J10" metaid="_Sluka0052" name="J10" reversible="false" sboTerm="SBO:0000185">
1231 <notes>
1232 <body xmlns="http://www.w3.org/1999/xhtml">
1233 <p>Blood born transfer of compound from the Liver compartment (CLiver) to the Venous compartment (CVen) in moles/hour.</p>
1234 </body>
1235
1236 </notes>
1237 <listOfReactants>
1238 <speciesReference metaid="_8ac2cd72-6ab2-457a-9007-6daa29a5db8e" species="CLiver" stoichiometry="1"/>
1239 </listOfReactants>
1240 <listOfProducts>
1241 <speciesReference metaid="_1096935b-7858-4617-9e75-2afe1772cda9" species="CVen" stoichiometry="1"/>
1242 </listOfProducts>
1243 <kineticLaw metaid="_5d8992d1-b2d1-4d5f-8659-45b82025677c">
1244 <math xmlns="http://www.w3.org/1998/Math/MathML">
1245 <apply>
1246 <divide/>
1247 <apply>
1248 <times/>
1249 <apply>
1250 <times/>
1251 <apply>
1252 <divide/>
1253 <apply>
1254 <plus/>
1255 <ci> QLiver </ci>
1256 <ci> QGut </ci>
1257 </apply>
1258 <ci> VLiver </ci>
1259 </apply>
1260 <ci> CLiver </ci>
1261 </apply>
1262 <ci> Ratioblood2plasma </ci>
1263 </apply>
1264 <apply>
1265 <times/>
1266 <ci> Kliver2plasma </ci>
1267 <ci> Fraction_unbound_plasma </ci>
1268 </apply>
1269 </apply>
1270 </math>
1271 </kineticLaw>
1272 </reaction>
1273 <reaction id="J11" metaid="_Sluka0053" name="J11" reversible="false" sboTerm="SBO:0000185">
1274 <notes>
1275 <body xmlns="http://www.w3.org/1999/xhtml">
1276 <p>Blood born transfer of compound from the Arterial compartment (CArt) to the Kidney compartment (CKidney) in moles/hour.</p>
1277 </body>
1278
1279 </notes>
1280 <listOfReactants>
1281 <speciesReference metaid="_3f6f102f-960b-4535-abad-c9dcab37f5af" species="CArt" stoichiometry="1"/>
1282 </listOfReactants>
1283 <listOfProducts>
1284 <speciesReference metaid="fcdceb02-27cf-4eaf-9735-149ce13b8fcf" species="CKidney" stoichiometry="1"/>
1285 </listOfProducts>
1286 <kineticLaw metaid="_817e3503-2c9a-4ac7-bf26-a86c0df69736">
1287 <math xmlns="http://www.w3.org/1998/Math/MathML">
1288 <apply>
1289 <times/>
1290 <apply>
1291 <divide/>
1292 <ci> QKidney </ci>
1293 <ci> VArt </ci>
1294 </apply>
1295 <ci> CArt </ci>
1296 </apply>
1297 </math>
1298 </kineticLaw>
1299 </reaction>
1300 <reaction id="J12" metaid="_Sluka0054" name="J12" reversible="false" sboTerm="SBO:0000185">
1301 <notes>
1302 <body xmlns="http://www.w3.org/1999/xhtml">
1303 <p>Transfer of compound from the Kidney compartment (CKidney) to the Kidney tubules (species CTubules
1304 in the compartment "KidenyTubules") in moles/hour.</p>
1305 </body>
1306
1307 </notes>
1308 <listOfReactants>
1309 <speciesReference metaid="_99b63060-427c-457a-b9af-5da81081e566" species="CKidney" stoichiometry="1"/>
1310 </listOfReactants>
1311 <listOfProducts>
1312 <speciesReference metaid="_31a97709-72f0-475c-ba47-cb5f995a9b72" species="CTubules" stoichiometry="1"/>
1313 </listOfProducts>
1314 <kineticLaw metaid="d3875b3e-a109-4a9f-bd96-667c0cfa48dc">
1315 <math xmlns="http://www.w3.org/1998/Math/MathML">
1316 <apply>
1317 <divide/>
1318 <apply>
1319 <times/>
1320 <apply>
1321 <divide/>
1322 <ci> Qgfr </ci>
1323 <ci> VKidney </ci>
1324 </apply>
1325 <ci> CKidney </ci>
1326 </apply>
1327 <ci> Kkidney2plasma </ci>
1328 </apply>
1329 </math>
1330 </kineticLaw>
1331 </reaction>
1332 <reaction id="J13" metaid="_Sluka0055" name="J13" reversible="false" sboTerm="SBO:0000185">
1333 <notes>
1334 <body xmlns="http://www.w3.org/1999/xhtml">
1335 <p>Blood born transfer of compound from the Kidney compartment (CKidney) to the Venous compartment (CVen) in moles/hour.</p>
1336 </body>
1337
1338 </notes>
1339 <listOfReactants>
1340 <speciesReference metaid="e48d0b0a-8264-44ab-8753-98e477b9beab" species="CKidney" stoichiometry="1"/>
1341 </listOfReactants>
1342 <listOfProducts>
1343 <speciesReference metaid="_4ef43c92-7ebd-4b57-8520-28e20e922adc" species="CVen" stoichiometry="1"/>
1344 </listOfProducts>
1345 <kineticLaw metaid="_3124b0be-11ac-4c82-b3ca-c944af1372c6">
1346 <math xmlns="http://www.w3.org/1998/Math/MathML">
1347 <apply>
1348 <divide/>
1349 <apply>
1350 <times/>
1351 <apply>
1352 <times/>
1353 <apply>
1354 <divide/>
1355 <ci> QKidney </ci>
1356 <ci> VKidney </ci>
1357 </apply>
1358 <ci> CKidney </ci>
1359 </apply>
1360 <ci> Ratioblood2plasma </ci>
1361 </apply>
1362 <apply>
1363 <times/>
1364 <ci> Kkidney2plasma </ci>
1365 <ci> Fraction_unbound_plasma </ci>
1366 </apply>
1367 </apply>
1368 </math>
1369 </kineticLaw>
1370 </reaction>
1371 </listOfReactions>
1372 </model>
1373 </sbml>
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