Pharmacokinetics of two novel rectal controlled-release morphine formulations

Administration of morphine by the oral route is not possible in cancer patients who are unable to swallow or are intolerant of oral morphine. Thus, there is a need for reliable alternate routes of drug administration. We compared the bioavailability of two prototype 30-mg morphine sulfate controlled-release suppository formulations (high and low viscosity) with 30-mg oral controlled-release morphine sulfate tablets in a 14-subject single-dose randomized, three-way crossover study. Venous blood samples were obtained immediately prior to and for 24 hr following each dose. Morphine concentrations were determined by radioimmunoassay. Compared with oral controlled-release morphine, the high- and low-viscosity suppository formulations had significantly greater bioavailability (AUC 0–24 72.7± 13.2 for the oral preparation versus 98.6±35.7 and 105.8±37.3 ng · hr/mL for the suppositories, respectively, P < 0.05), later peak concentration (t max 2.3±0.8 versus 3.1±2.3 and 5.0±1.5 hr, respectively, P < 0.05), and longer half-value duration (4.3±1.6 versus 10.4±5.5 and 9.5±4.3 hr, respectively, P < 0.05). Peak concentration for the high-viscosity suppository formulation (C max 7.75±2.66 ng/mL) was significantly lower than the low-viscosity suppository (C max 9.23±2.85 ng/mL) and the oral tablet (C max 10.4±2.78 ng/mL) formulations ( P < 0.05). The increased bioavailability observed with the two controlled-release suppositories may be the result of partial avoidance of hepatic biotransformation with rectal administration.