Simulated values of the mean plasma CL (liters · h−1) and V (liters) of M3G in rats after an acute dose of i.v. morphine alone (Group 1) compared with rats dosed acutely with parenteral chloramphenicol plus morphine (Group 2) where the proportion of the morphine dose metabolized to M3G is progressively decreased from 73% as reported by Evans and Shanahan (1995) to 25%, with a constant M3G AUC value.
| Dosing Regime (Chronic Studies) | % Dose Metabolized to M3G | MeanCL | Mean V |
|---|---|---|---|
| liters · h−1 | liters | ||
| Saline/Morphine | 73 | 2.08 ± 0.65 | 1.37 ± 0.23 |
| Chloramphenicol/Morphine | 73 | 1.19 ± 0.21 | 1.82 ± 0.23 |
| Chloramphenicol/Morphine | 50 | 0.82 ± 0.14 | 1.25 ± 0.16 |
| Chloramphenicol/Morphine | 36.5 | 0.48 ± 0.13 | 0.71 ± 0.16 |
| Chloramphenicol/Morphine | 25 | 0.41 ± 0.07 | 0.62 ± 0.08 |
These data clearly show that if the M3G AUC value doesn't change, any decrease in the volume of distribution of M3G will effectively mask a concomitant decrease in the metabolism of morphine to M3G.