Bioequivalence study on two different sustained release morphine formulations

The purpose of this study, performed on cancer patients requiring treatment with morphine, was to assess the comparative bioavailability, effectiveness and tolerability of SR Morphine Sulphate (MSSR) with respect to a different sustained release formulation (MS Contin) in steady-state conditions. MSSR gelatinous, sustained release capsules have shown themselves to achieve good therapeutic results with only two daily administrations, whereas morphine syrup requires 4-6. To perform the bioequivalence test after repeated administrations, 12 hospitalized or out patients of both sexes, and more than 18 years old were selected. All were suffering from stable cancer pathologies with pain from neoplasms of such intensity as to require the use of strong opiates according to the criteria established by the World Health Organization. After a period of stabilization of the morphine syrup posology (seven days), the products were administered at random to each patient with a posology of 60 mg, twice a day, for a period of six days using a cross-over scheme. The treatments were performed after a wash-out of 2 days with morphine syrup. Samples of venous blood were taken at the first and sixth day at 0, 15, 30 minutes and 1, 2, 4, 6, 8 and 12 hours from the morning administration. The plasmatic levels of morphine were determined by means of HPLC. Pharmacokinetic parameters AUC, Tmax, and Cmax, were analyzed statistically by means of a Westlake test. The pharmacokinetic parameters were calculated and analysed statistically so far as concerns the curves relative to the first and last treatment.