Comparative Single-Dose Pharmacokinetics of Sustained-Release and Modified-Release Morphine Sulfate Capsules Under Fed and Fasting Conditions

Abstract

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™) and sustained-release capsules (Kapanol™). 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™ was bio-equivalent fed and fasting, and under fasting conditions Kapanol™ and MXL™ were bioequivalent. In contrast, MXL™ was not bioequivalent under fed and fasting conditions. Although Kapanol™ and MXL™ showed similar oral bioavailability [area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax)], the time to Cmax (tmax) of Kapanol™ was significantly longer than that of MXL™. Food significantly prolonged the tmax of Kapanol™ but had no effect on the extent of absorption or Cmax. In contrast, both the rate and extent of absorption of morphine from MXL™ were significantly reduced with food. In conclusion, Kapanol™ both fed and fasting has a superior sustained-release pharmacokinetic profile for a formulation designed for once-a-day administration compared with MXL™. Because food does not impair the bioavailability of Kapanol™, it can be taken without regard to meals.