A BIOEQUIVALENCE STUDY OF ORAL CONTROLLED-RELEASE MORPHINE USING NALTREXONE BLOCKADE

Twenty-three normal volunteers who received morphine sulphate (MS Cont in) with naltrexone completed this randomized, analytically blinded, t wo-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 10O-mg MSC tablets , Morphine effects were blocked by three 100-mg doses of naltrexone, T he first dose of naltrexone was given 24 hours before MSC dosing, foll owed by a second dose at the time of MSC dosing and a third dose 24 ho urs after MSC administration. Compared with two 100-mg MSC tablets, th e 200-mg tablet was 96% bioavailable (90% confidence interval, 88.14-1 05.74%). The 90% confidence intervals for mean C-max and AUC(0-24) for one 200-mg MSC tablet were within +/-20% of the C-max and AUC(0-24), of two 100-mg tablets, indicating the two dosage forms are bioequivale nt. Single 200-mg doses of MSC given with the naltrexone blockade were generally well tolerated, and adverse effects were similar to those r eported for naltrexone alone and for lower doses of morphine without n altrexone, Naltrexone proved safe and effective in blocking the effect s of controlled-release morphine, permitting bioequivalence studies of a high dose of morphine in normal volunteers.