Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation.

Abstract

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.