Teeguarden
Notes
BPA/BPAG PBPK (Human; Teeguarden et al., 2005) Human PBK for oral absorption administration → GITract Lumen → liver <- GITract Lumen Metabolism Parent only, perfusion-limited tissues GITract Lumen Metabolism BAPG → BAP Hepatic Metabolism BAP → BAPG EHR of BAPG
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) | no routes detected |
| Time resolution | h |
| Amounts unit | mg |
| Volume unit | L |
| Number of compartments | 5 |
| Number of species | 8 |
| Number of parameters | 30 (15 external / 15 internal) |
Diagram
Compartments
| id | name | unit | model qualifier |
|---|---|---|---|
| GILumen | GI lumen compartment | L | http://purl.obolibrary.org/obo/PBPKO_00478 |
| 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 |
| Feces | feces | L | http://purl.obolibrary.org/obo/PBPKO_00555 |
Species
| id | name | unit | model qualifier |
|---|---|---|---|
| AGILumen | Amount in GI lumen | mg | http://purl.obolibrary.org/obo/PBPKO_00496 |
| ALiver | amount of chemical in liver | mg | http://purl.obolibrary.org/obo/PBPKO_00497 |
| ABlood | amount of chemical in blood | mg | http://purl.obolibrary.org/obo/PBPKO_00623 |
| ARest | amount of chemical in rest-of-body | mg | http://purl.obolibrary.org/obo/PBPKO_00501 |
| ALiverMet | Amount of metabolite in liver | mg | http://purl.obolibrary.org/obo/PBPKO_00497 |
| AGILumenMet | Amount of metabolite in GI lumen | mg | http://purl.obolibrary.org/obo/PBPKO_00496 |
| ABloodMet | Amount of metabolite in blood | mg | http://purl.obolibrary.org/obo/PBPKO_00623 |
| AFecesMet | Amount of metabolite in feces | mg | http://purl.obolibrary.org/obo/PBPKO_00273 |
Transfer equations
| id | from | to | equation |
|---|---|---|---|
| _J0 | AGILumen | ALiver | kabsMet1 * AGILumen |
| _J1 | ABlood | ALiver | QL * CBlood |
| _J2 | ALiver | ABlood | QL * CLiver / PL |
| _J3 | ABlood | ARest | QRest * CBlood |
| _J4 | ARest | ABlood | QRest * CRest / PRest |
| _J5 | ALiver | ALiverMet | MWMet / MW * (VmaxLMet * (CLiver / PL) / (KmLMet + CLiver / PL)) |
| _J6 | ALiverMet | ABloodMet | (1 - BileFrac) * ALiverMet |
| _J7 | ALiverMet | AGILumenMet | BileFrac * ALiverMet |
| _J8 | AGILumenMet | ALiver | AGILumenMet * kehrMet1 |
| _J9 | AGILumenMet | AFecesMet | AGILumenMet * kfe |
ODEs
\(\frac{d[\mathtt{AGILumen}]}{dt} = - \mathit{kabsMet1}\cdot \mathit{AGILumen}\)
\(\frac{d[\mathtt{ALiver}]}{dt} = \mathit{kabsMet1}\cdot \mathit{AGILumen} + \mathit{QL}\cdot \mathit{CBlood} - \frac{\mathit{QL}\cdot \mathit{CLiver}}{\mathit{PL}} - \frac{\mathit{MWMet}}{\mathit{MW}}\cdot \frac{\mathit{VmaxLMet}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet}+\frac{\mathit{CLiver}}{\mathit{PL}}} + \mathit{AGILumenMet}\cdot \mathit{kehrMet1}\)
\(\frac{d[\mathtt{ABlood}]}{dt} = - \mathit{QL}\cdot \mathit{CBlood} + \frac{\mathit{QL}\cdot \mathit{CLiver}}{\mathit{PL}} - \mathit{QRest}\cdot \mathit{CBlood} + \frac{\mathit{QRest}\cdot \mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{ARest}]}{dt} = \mathit{QRest}\cdot \mathit{CBlood} - \frac{\mathit{QRest}\cdot \mathit{CRest}}{\mathit{PRest}}\)
\(\frac{d[\mathtt{ALiverMet}]}{dt} = \frac{\mathit{MWMet}}{\mathit{MW}}\cdot \frac{\mathit{VmaxLMet}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet}+\frac{\mathit{CLiver}}{\mathit{PL}}} - (1-\mathit{BileFrac})\cdot \mathit{ALiverMet} - \mathit{BileFrac}\cdot \mathit{ALiverMet}\)
\(\frac{d[\mathtt{AGILumenMet}]}{dt} = \mathit{BileFrac}\cdot \mathit{ALiverMet} - \mathit{AGILumenMet}\cdot \mathit{kehrMet1} - \mathit{AGILumenMet}\cdot \mathit{kfe}\)
\(\frac{d[\mathtt{ABloodMet}]}{dt} = (1-\mathit{BileFrac})\cdot \mathit{ALiverMet}\)
\(\frac{d[\mathtt{AFecesMet}]}{dt} = \mathit{AGILumenMet}\cdot \mathit{kfe}\)
Assignment rules
| variable | assignment |
|---|---|
| VL | VLc * BW |
| VB | VBc * BW |
| VRest | 0.84 * BW - VL - VB |
| QC | QCc * pow(BW, 0.75) |
| QLc | 0.23 |
| QL | QLc * QC |
| QRest | (1 - QLc) * QC |
| kabsMet1 | kabsMet1C * pow(BW, -0.25) |
| VmaxLMet | VmaxLMetC * pow(BW, 0.75) |
| kehrMet1 | kehrMet1C * pow(BW, -0.25) |
| kfe | kfeC * pow(BW, -0.25) |
| CBlood | ABlood / Blood |
| CLiver | ALiver / Liver |
| CRest | ARest / Rest |
| CPlasma | CBlood / RBP |
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 |
| QCc | Cardiac output constant | L/h/kg^0.75 | http://purl.obolibrary.org/obo/PBPKO_00013 |
| 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 |
| QL | Blood flow rate to liver | L/h | http://purl.obolibrary.org/obo/PBPKO_00024 |
| QRest | Blood flow 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 |
| RBP | Blood plasma ratio | dimensionless | http://purl.obolibrary.org/obo/PBPKO_00187 |
| kabsMet1C | Intrinsic uptake from stomach to liver constant | not specified | not specified |
| kabsMet1 | Uptake rate from stomach to liver | /h | not specified |
| VmaxLMetC | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| VmaxLMet | Glucuronidation - Vmax | not specified | http://purl.obolibrary.org/obo/PBPKO_00214 |
| KmLMet | Glucuronidation - Km | mg/L | http://purl.obolibrary.org/obo/PBPKO_00214 |
| MW | Molecular weight | g/mol | http://purl.obolibrary.org/obo/PBPKO_00127 |
| MWMet | Molecular weight | g/mol | http://purl.obolibrary.org/obo/PBPKO_00127 |
| BileFrac | % of metabolite that goes to bile | dimensionless | not specified |
| kehrMet1C | Enterohepatic recirculation constant metabolite | not specified | not specified |
| kehrMet1 | Enterohepatic recirculation rate of metabolite | /h | not specified |
| kfeC | Fecal elimination constant | not specified | http://purl.obolibrary.org/obo/PBPKO_00236 |
| kfe | Fecal elimination rate | /h | http://purl.obolibrary.org/obo/PBPKO_00230 |
| CBlood | Concentration in blood | mg/L | http://purl.obolibrary.org/obo/PBPKO_00301 |
| CLiver | Concentration in liver | mg/L | http://purl.obolibrary.org/obo/PBPKO_00539 |
| CRest | Concentration in rest of body | mg/L | http://purl.obolibrary.org/obo/PBPKO_00548 |
| CPlasma | Concentration in plasma | mg/L | http://purl.obolibrary.org/obo/PBPKO_00549 |