Study on the pharmacokinetics of a controlled-release morphine sulfate tablet (MS contin) in cancer patients.

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MS Cohtin (MS-C) is a controlled-release tablet of morphine sulfate developed by Muhdipharma AG, Switzerland, for the purpose of maintaining the blood concentration of morphine in an effective analgesic range by administration every 12 hr. In this study, the pharmacokihetics of morphine (M), and its metabolites, morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G), were investigated in patients with cancer pain at steady state following oral administration of MS-C. MS-C was administered every 12 hr, with the dose being adjusted so as to control each patient's pain. In the patients administered MS-C at doses of 20, 30, or 40 mg every 12 hr, the plasma concentrations of M, M-6-G, and M-3-G showed broad hill-like patterns over a period of 12 hr with the peaks occurring at 4 hr. The plasma cohcentrations were found to be almost proportional to the doses. Cmax and AUC values of M, M-6-G, and M-3-G were also almost proportional to the doses, and t1/2 (kab), t1/2 (kel), τ, and Tmax values were comparable between the doses. Total urihary recovery rates from 24-hr urine and the recovery rates for M, M-6-G, and M-3-G were comparable between the doses. These results indicate that there is no significant change in the pharmacokinetics following MS-C administration at various doses in cancer patients.
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