Sharma
Notes
BAP PBK (Sharma 2018): Human PBK for oral absorption (administration → stomach → gut → liver → blood) Parent only, perfusion-limited tissues Intestinal Metabolism BAP → BAPG Hepatic Metabolism BAP → BAPG and BAPS
Overview
| key | value |
|---|---|
| Modelled species/orgamism(s) | not specified |
| Model chemical(s) | not specified |
| Input route(s) | 1 (oral) |
| Time resolution | h |
| Amounts unit | umol |
| Volume unit | L |
| Number of compartments | 5 |
| Number of species | 8 |
| Number of parameters | 38 (19 external / 19 internal) |
Diagram
Compartments
| id | name | unit | model qualifier |
|---|---|---|---|
| Stomach | stomach | L | http://purl.obolibrary.org/obo/PBPKO_00566 |
| Liver | liver | L | http://purl.obolibrary.org/obo/PBPKO_00558 |
| Plasma | blood plasma | L | http://purl.obolibrary.org/obo/PBPKO_00488 |
| Gut | gut | L | http://purl.obolibrary.org/obo/PBPKO_00477 |
| Rest | rest-of-body | L | http://purl.obolibrary.org/obo/PBPKO_00450 |
Species
| id | name | unit | model qualifier |
|---|---|---|---|
| ASt | not specified | not specified | not specified |
| ALiver | amount of chemical in liver | umol | http://purl.obolibrary.org/obo/PBPKO_00497 |
| APlasma | amount of chemical in plasma | umol | http://purl.obolibrary.org/obo/PBPKO_00502 |
| AGut | amount of chemical in gut | umol | http://purl.obolibrary.org/obo/PBPKO_00496 |
| ARest | amount of chemical in rest-of-body | umol | http://purl.obolibrary.org/obo/PBPKO_00501 |
| AGutMet1 | Amount in gut | umol | http://purl.obolibrary.org/obo/PBPKO_00496 |
| ALiverMet1 | Amoun in liver | umol | http://purl.obolibrary.org/obo/PBPKO_00497 |
| ALiverMet2 | Amount in liver | umol | http://purl.obolibrary.org/obo/PBPKO_00497 |
Transfer equations
| id | from | to | equation |
|---|---|---|---|
| _J0 | ASt | AGut | ksto * ASt |
| _J1 | ASt | ALiver | k0 * ASt |
| _J2 | AGut | ALiver | kabs * AGut |
| _J3 | AGut | AGutMet1 | VmaxGMet1 * CGut * fup / (CGut * fup + KmGMet1) |
| _J4 | APlasma | ALiver | QL * CPlasma * fup |
| _J5 | ALiver | APlasma | QL * fup * CLiver / PL |
| _J6 | APlasma | ARest | QRest * CPlasma * fup |
| _J7 | ARest | APlasma | QRest * fup * CRest / PRest |
| _J8 | ALiver | ALiverMet1 | VmaxLMet1 * CLiver * fup / (CLiver * fup + KmLMet1) |
| _J9 | ALiver | ALiverMet2 | VmaxLMet2 * CLiver * fup / (CLiver * fup + KmLMet2) |
ODEs
\(\frac{d[\mathtt{ASt}]}{dt} = - \mathit{ksto}\cdot \mathit{ASt} - \mathit{k0}\cdot \mathit{ASt}\)
\(\frac{d[\mathtt{ALiver}]}{dt} = \mathit{k0}\cdot \mathit{ASt} + \mathit{kabs}\cdot \mathit{AGut} + \mathit{QL}\cdot \mathit{CPlasma}\cdot \mathit{fup} - \frac{\mathit{QL}\cdot \mathit{fup}\cdot \mathit{CLiver}}{\mathit{PL}} - \frac{\mathit{VmaxLMet1}\cdot \mathit{CLiver}\cdot \mathit{fup}}{\mathit{CLiver}\cdot \mathit{fup}+\mathit{KmLMet1}} - \frac{\mathit{VmaxLMet2}\cdot \mathit{CLiver}\cdot \mathit{fup}}{\mathit{CLiver}\cdot \mathit{fup}+\mathit{KmLMet2}}\)
\(\frac{d[\mathtt{APlasma}]}{dt} = - \mathit{QL}\cdot \mathit{CPlasma}\cdot \mathit{fup} + \frac{\mathit{QL}\cdot \mathit{fup}\cdot \mathit{CLiver}}{\mathit{PL}} - \mathit{QRest}\cdot \mathit{CPlasma}\cdot \mathit{fup} + \frac{\mathit{QRest}\cdot \mathit{fup}\cdot \mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{AGut}]}{dt} = \mathit{ksto}\cdot \mathit{ASt} - \mathit{kabs}\cdot \mathit{AGut} - \frac{\mathit{VmaxGMet1}\cdot \mathit{CGut}\cdot \mathit{fup}}{\mathit{CGut}\cdot \mathit{fup}+\mathit{KmGMet1}}\)
\(\frac{d[\mathtt{ARest}]}{dt} = \mathit{QRest}\cdot \mathit{CPlasma}\cdot \mathit{fup} - \frac{\mathit{QRest}\cdot \mathit{fup}\cdot \mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{AGutMet1}]}{dt} = \frac{\mathit{VmaxGMet1}\cdot \mathit{CGut}\cdot \mathit{fup}}{\mathit{CGut}\cdot \mathit{fup}+\mathit{KmGMet1}}\)
\(\frac{d[\mathtt{ALiverMet1}]}{dt} = \frac{\mathit{VmaxLMet1}\cdot \mathit{CLiver}\cdot \mathit{fup}}{\mathit{CLiver}\cdot \mathit{fup}+\mathit{KmLMet1}}\)
\(\frac{d[\mathtt{ALiverMet2}]}{dt} = \frac{\mathit{VmaxLMet2}\cdot \mathit{CLiver}\cdot \mathit{fup}}{\mathit{CLiver}\cdot \mathit{fup}+\mathit{KmLMet2}}\)
Assignment rules
| variable | assignment |
|---|---|
| VL | VLc * BW |
| VPlasma | VPlasmac * BW |
| VG | VGc * BW |
| VRest | 0.84 * BW - VL - VPlasma - VG |
| QC | 20 * pow(BW, 0.75) |
| QL | QLc * QC |
| QG | QGc * QC |
| QRest | (1 - QLc - QGc) * QC |
| k0 | k0C * pow(BW, -0.25) |
| ksto | kstoC * pow(BW, -0.25) |
| kabs | kabsC * pow(BW, -0.25) |
| VmaxGMet1 | 22750 / 1000 * pow(BW, 0.75) |
| VmaxLMet1 | 680095.6 / 1000 * pow(BW, 0.75) |
| VmaxLMet2 | 11657 / 1000 * pow(BW, 0.75) |
| CLiver | ALiver / Liver |
| CPlasma | APlasma / Plasma |
| CPlasma_Total | CPlasma / fup |
| CGut | AGut / Gut |
| CRest | ARest / Rest |
Initial assignments
| variable | assignment |
|---|---|
| Liver | VL |
| Plasma | VPlasma |
| Gut | VG |
| Rest | VRest |
Parameters
| id | name | unit | model qualifier |
|---|---|---|---|
| BW | body weight | kg | http://purl.obolibrary.org/obo/PBPKO_00008 |
| VLc | Volume fraction of liver to bodyweight | L/kg | http://purl.obolibrary.org/obo/PBPKO_00078 |
| VPlasmac | Volume fraction of plasma to bodyweight | L/kg | http://purl.obolibrary.org/obo/PBPKO_00104 |
| VGc | Volume fraction of gut to bodyweight | L/kg | http://purl.obolibrary.org/obo/PBPKO_00509 |
| VL | Volume of liver | L | http://purl.obolibrary.org/obo/PBPKO_00077 |
| VPlasma | Volume of plasma | L | http://purl.obolibrary.org/obo/PBPKO_00103 |
| VG | Volume of gut | L | http://purl.obolibrary.org/obo/PBPKO_00524 |
| VRest | Volume of rest of body | L | http://purl.obolibrary.org/obo/PBPKO_00105 |
| QC | Cardiac output | L/h | http://purl.obolibrary.org/obo/PBPKO_00013 |
| QLc | Blood flow to liver constant | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00025 |
| QGc | Blood flow to gut constant | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00513 |
| QL | Blood flow rate to liver | L/h | http://purl.obolibrary.org/obo/PBPKO_00024 |
| QG | Blood flow rate to gut | L/h | http://purl.obolibrary.org/obo/PBPKO_00531 |
| QRest | Blood flow rate to rest of body | L/h | http://purl.obolibrary.org/obo/PBPKO_00050 |
| Hct | Hematocrit | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00527 |
| fup | unbound fraction | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00149 |
| k0C | Intrinsic stomach absorption rate constant | not specified | not specified |
| k0 | Stomach absorption rate constant | /h | not specified |
| kstoC | intrinsic gastric emptying rate constant | not specified | not specified |
| ksto | Gastric emptying rate | /h | http://purl.obolibrary.org/obo/PBPKO_00143 |
| kabsC | intrinsic absorption rate constant | not specified | not specified |
| kabs | Oral absorption rate | /h | not specified |
| VmaxGMet1C | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00212 |
| VmaxGMet1 | Glucuronidation - Vmax | umol/h/kg | http://purl.obolibrary.org/obo/PBPKO_00212 |
| KmGMet1 | Glucuronidation - Km | umol | http://purl.obolibrary.org/obo/PBPKO_00212 |
| VmaxLMet1C | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet1 | Glucuronidation - Vmax | umol/h/kg | http://purl.obolibrary.org/obo/PBPKO_00214 |
| KmLMet1 | Glucuronidation - Km | umol | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet2C | Sulfation - Vmax | umol/h/kg | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet2 | Sulfation - Vmax | umol/h/kg | http://purl.obolibrary.org/obo/PBPKO_00214 |
| KmLMet2 | Sulfation - Km | umol | http://purl.obolibrary.org/obo/PBPKO_00214 |
| PL | Partition coefficient - liver | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00577 |
| PRest | Partition coefficient - rest of body | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00585 |
| CLiver | Concentration in liver | umol/L | http://purl.obolibrary.org/obo/PBPKO_00539 |
| CPlasma | Concentration in plasma | umol/L | http://purl.obolibrary.org/obo/PBPKO_00549 |
| CPlasma_Total | Concentration in plasma | umol/L | http://purl.obolibrary.org/obo/PBPKO_00549 |
| CGut | Concentration in gut | umol/L | http://purl.obolibrary.org/obo/PBPKO_00538 |
| CRest | Concentration in rest of body | umol/L | http://purl.obolibrary.org/obo/PBPKO_00548 |