Fit to two-compartment model for M and MG (mi) after intravenous (14.9 ± 1.6 μmol·kg−1) and intraduodenal (26.6 ± 0.40 μmol·kg−1) doses of morphine sulfate to the rat (305 ± 16 g)
Fitted estimates are percent CV values expressed within parentheses.
| Parameter | Definition | Individual Fitted Value | Population Fitted Value |
|---|---|---|---|
| k12 (min−1) | First-order transfer rate constant between central and peripheral compartments | 0.404 (46.9) | 0.363 (46.4) |
| k21 (min−1) | 0.143 (72.9) | 0.113 (69.5) | |
| k10 (min−1)a | First-order elimination constant from central compartment | 0.0711 | 0.0735 |
| km (min−1) | First-order rate constant describing formation of MG from M | 0.048 (24.3) | 0.047 (20.9) |
| km,others (min−1) | First-order rate constant describing forming other metabolites from M | 0.001 (24.1) | 0.001 (25.0) |
| kbile (min−1) | First-order rate constant describing biliary secretion of M | 0.0001 (31.0) | 0.0004 (31.0) |
| krenal (min−1) | First-order rate constant describing renal excretion of M | 0.022 (26.8) | 0.021 (23.6) |
| V1 (ml) | Volume of distribution of central compartment for M | 140 (59.1) | 120 (58.0) |
| ka (min−1) | First-order absorption rate constant of M | 0.036 (37.3) | 0.034 (35.2) |
| CLtot (ml·min−1) | Total clearance of M | 9.95 | 8.82 |
| gmi = km/k10 | Fraction of total morphine clearance responsible for forming MG | 0.675 | 0.642 |
| Fabs | Fraction of dose absorbed | 0.94 (30.0) | 0.95 (24.8) |
| k{mi}bile (min−1) | First-order rate constant describing biliary excretion of MG | 0.045 (59.1) | 0.040 (46.4) |
| k{mi}renal (min−1)b | First-order rate constant describing renal excretion of MG | 0.020 (12.5) | 0.020 (12.1) |
| V{mi} (ml) | Volume of distribution of metabolite compartment | 306 (36.0) | 292 (29.8) |