Table 1.
Pharmacokinetic parameters for MTX and MTXPGn in healthy and CIA rats
| Parameter (units) | Definition | Estimate | CV% |
|---|---|---|---|
| ka (hr−1) | First-order absorption rate | 3.69 | FIXEDa |
| CLe (L/hr/kg) | Systemic clearance | 0.409 | 9.05 |
| V1 (L/kg) | Volume of central compartment | 0.174 | 16.4 |
| CLd (L/hr/kg) | Distribution clearance | 0.0707 | 19.8 |
| V2 (L/kg) | Volume of peripheral compartment | 0.326 | 35.8 |
| CLpr (L/hr/kg) | Influx clearance of MTX from V1 to RBC | 0.000979 | 19.8 |
| CL12 (L/hr/kg) | Metabolic clearance of MTX to MTXPG2 in RBC | 0.00000491 | 7.04 |
| CL13 (L/hr/kg) | Metabolic clearance of MTX to MTXPG3 in RBC | 0.00000958 | 6.18 |
| CLrp (L/hr/kg) | Efflux clearance of MTX from RBC to V1 | 0.000289 | 18.5 |
| V3 (L/kg) | Volume of RBC | 0.024 | Fixedb |
| kpr (hr−1) | Influx rate constant of MTX from V1 to RBC | 0.00564 | c |
| k12 (hr−1) | Metabolic rate constant of MTX to MTXPG2 in RBC | 0.00020 | c |
| k23 (hr−1) | Metabolic rate constant of MTX to MTXPG3 in RBC | 0.0004 | c |
| krp (hr−1) | Efflux rate constant of MTX from RBC to V1 | 0.0120 | c |
a
Parameter fixed to value scaled from monkeys and human data in literature
b
Parameter fixed to value from healthy rats in literature
c
Secondary parameter