RELATIVE BIOAVAILABILITY OF CONTROLLED-RELEASE ORAL MORPHINE-SULFATE DURING NALTREXONE BLOCKADE

The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was det ermined using a randomized, 2-way crossover, analytically blinded stud y design. Although naltrexone did not qualitatively alter the concentr ation-time curve for controlled-release morphine, the area under the p lasma morphine concentration-time curve from 0 - 24 h (AUC(0-24)) was significantly greater (p < 0.01) for morphine given with naltrexone (2 65 ngxh/ml) than for morphine given alone (215 ngxh/ml). Compared to m orphine given alone, the apparent absorption half-life of morphine was decreased from 0.94 - 0.58 h (p = 0.01) and C-max was increased from 28.17 ng/ml to 32.26 ng/ml (p = 0.04) during naltrexone blockade, wher eas the T-max and apparent elimination half-life of morphine were not significantly affected. The minimal differences in morphine bioavailab ility indicate naltrexone may be useful in comparative bioavailability studies of high-dose opioids in opioid-naive normal volunteers.