Comparative single-dose pharmacokinetics of sustained-release and modified-release morphine sulfate capsules under fed and fasting conditions

A randomised, single-dose, open-label, crossover study in 24 healthy male and female volunteers evaluated the pharmacokinetic profile and relative bioavailability under fed and fasting conditions of the 2 oral morphine sulfate formulations, modified-release capsules (MXL(TM)) and sustained-release capsules (Kapanol(TM)). A 60mg dose of study medication was administered 7 days apart after either an overnight fast of 10 hours or after a standard high-fat meal. Blood samples were taken for 48 hours postdose and were analysed for morphine by high-performance liquid chromatography using electrochemical detection. Kapanol(TM) was bioequivalent fed and fasting, and under fasting conditions Kapanol(TM) and MXL(TM) were bioequivalent. In contrast, MXL(TM) was not bioequivalent under fed and fasting conditions. Although Kapanol(TM) and MXL(TM) showed similar oral bioavailability [area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (C-max)], the time to C-max (t(max)) of Kapanol(TM) was significantly longer than that of MXL(TM). Food significantly prolonged the t(max) of Kapanol(TM) but had no effect on the extent of absorption or C-max. In contrast, both the rate and extent of absorption of morphine from MXL(TM) were significantly reduced with food. In conclusion, Kapanol(TM) both fed and fasting has a superior sustained-release pharmacokinetic profile for a formulation designed for once-a-day administration compared with MXL(TM). Because food does not impair the bioavailability of Kapanol(TM), it can be taken without regard to meals.