The reproducibility of bioavailability of oral morphine from solution under fed and fasted conditions.

The reproducibility in bioavailability of orally administered morphine (as a solution) under fed and fasted conditions was studied in 5 patients with chronic pain on three occasions over 1 yr (0, 6, and 12 mo). During each study period (i.e.. 0, 6, and 12 mo), patients received the 50 mg oral dose both in the fasted state (10 hr since food) and immediately after a high fat content breakfast, in randomly determined sequence. Frequent blood samples were collected for 10 hr after the dose. There was no significant difference in the maximum blood morphine concentration (Cmax) or the time to Cmax among the three study periods or between the fed and fasted states. Bioavailability, as assessed by log(AUC), was significantly greater in the fed compared to the fasted state (P less than .01) but did not differ over the three study periods (Two-factor analysis of variance). Intrapatient variability contributed 32% and 54% to total variation in log(AUC) under fed and fasted conditions, respectively.