STUDY OF THE BIOEQUIVALENCE OF 2 CONTROLLED-RELEASE FORMULATIONS OF MORPHINE

The management and treatment of chronic pain in cancer patients is a c lear priority for practitioners regularly confronted by the situation. This investigation was carried out to evaluate the bioavailability of a recent sustained-release (SR) formulation of morphine sulphate (30 mg), Skenan, consisted of capsules, relative to a recognized product, Moscontin which is a matrix tablet SR form. The bioavailability was ca rried out on 12 healthy male volunteers who received a single dose (30 mg) of the test (T) and the recognized (R) products in a randomized b alanced 2-way crossover design. After dosing, serial blood samples wer e collected for a period of 24 hours. Morphine and its main metabolite s (i.e. glucuronides M6G and M3G) were assayed by high-performance liq uid chromatography using a ion-pair formation. Data were analyzed by a noncompartmental method and were compared by ANOVA method and, each s ubject taken as his own control, by the Wilcoxon T test. Mean bioavail ability of the T formulation was greater than that of R. The parametri c confidence intervals (90%) of the mean values of the pharmacokinetic s characteristics for T : R ratio were in each case without the bioequ ivalence acceptable ranges of 0.8 - 1.25 and 0.70 - 1.43 respectively for AUCs (i.e. AUC(0-->24h) and AUC(0-->infinity) and C-max, while con fidence intervals symmetric of Westlake (CIW90%) was invariably greate r than 20%, i.e. 62.8, 71.1 and 39.3% respectively. Further, the test formulation was not found bioequivalent to the reference formulation b y Schuirmann's 2 one-sided t-test. These results justify the conclusio n of the non-bioequivalence of the two forms at the unit dose of 30 mg . This information must be considered above all as a dosage adjustment tool enabling use of the two forms by application of a correction fac tor of the order of 15% when prescribing Skenan in comparison with Mos contin. Assessment is needed of the possible clinical consequences of this finding.