The clinical pharmacology of naltrexone: pharmacology and pharmacodynamics.

The time-action of opiate antagonist activity of naltrexone was evaluated in detoxified ex-opiate addicts, using 25 mg intravenous heroin challenges. A 100 mg naltrexone dose provided 96% blockade at 24 hr, 86.5% blockade at 48 hr and 46.6% blockade at 72 hr. Following oral administration, naltrexone was rapidly and completely absorbed. Peak levels of naltrexone and its major metabolite 6 beta-naltrexol were reached 1 hr after the dose. The high 6 beta-naltrexol plasma concentrations only 1 hr after drug administration indicate a rapid biotransformation process, converting a large fraction of the dose to less active metabolites. Over 70% of the dose was excreted in the 24 hr urine and less than 0.5% in the feces. No change was observed in the rate of naltrexone disposition during chronic dosing vs. the acute study, indicating no metabolic induction. The rapid achievement of steady state naltrexone plasma levels eliminates the need of stepwise induction at the beginning of naltrexone treatment.