Mielke
Notes
BPA PBPK (adult) after Mielke & Gundert-Remy 2009 # Perfusion-limited: Blood <-> Liver, Blood <-> Rest # Hepatic metabolism: BPA --UGT (BPAG), --SULT (BPAS)
Overview
| key | value |
|---|---|
| Modelled species/orgamism(s) | http://purl.obolibrary.org/obo/NCBITaxon_9606 |
| Model chemical(s) | http://purl.obolibrary.org/obo/CHEBI_33216 |
| Input route(s) | 1 (oral) |
| Time resolution | h |
| Amounts unit | umol |
| Volume unit | L |
| Number of compartments | 4 |
| Number of species | 6 |
| Number of parameters | 22 (11 external / 11 internal) |
Diagram
Compartments
| id | name | unit | model qualifier |
|---|---|---|---|
| Gut | gut | L | http://purl.obolibrary.org/obo/PBPKO_00477 |
| Liver | liver | L | http://purl.obolibrary.org/obo/PBPKO_00558 |
| Blood | blood | L | http://purl.obolibrary.org/obo/PBPKO_00464 |
| Rest | rest-of-body | L | http://purl.obolibrary.org/obo/PBPKO_00450 |
Species
| id | name | unit | model qualifier |
|---|---|---|---|
| AGut | amount of chemical in gut | umol | http://purl.obolibrary.org/obo/PBPKO_00496 |
| ALiver | amount of chemical in liver | umol | http://purl.obolibrary.org/obo/PBPKO_00497 |
| ABlood | amount of chemical in blood | umol | http://purl.obolibrary.org/obo/PBPKO_00623 |
| ARest | amount of chemical in rest-of-body | umol | http://purl.obolibrary.org/obo/PBPKO_00501 |
| ALiverMet1 | Amount 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 | AGut | ALiver | kabs * AGut |
| _J1 | ABlood | ALiver | QL * CBlood |
| _J2 | ALiver | ABlood | QL * (CLiver / PL) |
| _J3 | ABlood | ARest | QRest * CBlood |
| _J4 | ARest | ABlood | QRest * (CRest / PRest) |
| _J5 | ALiver | ALiverMet1 | VmaxLMet1 * (CLiver / PL) / (KmLMet1 + CLiver / PL) |
| _J6 | ALiver | ALiverMet2 | VmaxLMet2 * (CLiver / PL) / (KmLMet2 + CLiver / PL) |
ODEs
\(\frac{d[\mathtt{AGut}]}{dt} = - \mathit{kabs}\cdot \mathit{AGut}\)
\(\frac{d[\mathtt{ALiver}]}{dt} = \mathit{kabs}\cdot \mathit{AGut} + \mathit{QL}\cdot \mathit{CBlood} - \mathit{QL}\cdot \frac{\mathit{CLiver}}{\mathit{PL}} - \frac{\mathit{VmaxLMet1}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet1}+\frac{\mathit{CLiver}}{\mathit{PL}}} - \frac{\mathit{VmaxLMet2}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet2}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)
\(\frac{d[\mathtt{ABlood}]}{dt} = - \mathit{QL}\cdot \mathit{CBlood} + \mathit{QL}\cdot \frac{\mathit{CLiver}}{\mathit{PL}} - \mathit{QRest}\cdot \mathit{CBlood} + \mathit{QRest}\cdot \frac{\mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{ARest}]}{dt} = \mathit{QRest}\cdot \mathit{CBlood} - \mathit{QRest}\cdot \frac{\mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{ALiverMet1}]}{dt} = \frac{\mathit{VmaxLMet1}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet1}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)
\(\frac{d[\mathtt{ALiverMet2}]}{dt} = \frac{\mathit{VmaxLMet2}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet2}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)
Assignment rules
| variable | assignment |
|---|---|
| VL | VLc * BW |
| VB | VBc * BW |
| VRest | 0.84 * BW - VL - VB |
| QRest | QC - QL |
| VmaxLMet1 | VmaxLMet1C * 1800 * 60 / 1000 |
| VmaxLMet2C | 0.15 * VmaxLMet1C |
| VmaxLMet2 | VmaxLMet2C * 1800 * 60 / 1000 |
| CBlood | ABlood / Blood |
| CLiver | ALiver / Liver |
| CVL | CLiver / PL |
| CRest | ARest / Rest |
Initial assignments
| variable | assignment |
|---|---|
| Liver | VL |
| Blood | VB |
| 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 |
| VBc | Volume fraction of blood to bodyweight | L/kg | not specified |
| VL | Volume of liver | L | http://purl.obolibrary.org/obo/PBPKO_00077 |
| VB | Volume of blood | L | http://purl.obolibrary.org/obo/PBPKO_00108 |
| VRest | Volume of rest of body | L | http://purl.obolibrary.org/obo/PBPKO_00105 |
| QL | Blood flow rate to liver | L/h | http://purl.obolibrary.org/obo/PBPKO_00024 |
| QC | Cardiac output | L/h | http://purl.obolibrary.org/obo/PBPKO_00013 |
| QRest | Blood flow rate to rest of body | L/h | http://purl.obolibrary.org/obo/PBPKO_00050 |
| 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 |
| kabs | absorption constant rate | /h | not specified |
| KmLMet1 | Glucuronidation - Km | umol/L | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet1C | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet1 | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| KmLMet2 | Sulfation - Km | umol/L | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet2C | Sulfation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet2 | Sulfation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| CBlood | Concentration in blood | umol/L | http://purl.obolibrary.org/obo/PBPKO_00301 |
| CLiver | Concentration in liver | umol/L | http://purl.obolibrary.org/obo/PBPKO_00539 |
| CVL | Concentration in liver (Aliver/PL) | umol/L | http://purl.obolibrary.org/obo/PBPKO_00539 |
| CRest | Concentration in rest of body | umol/L | http://purl.obolibrary.org/obo/PBPKO_00548 |