ESTIMATION OF SYSTEMIC AVAILABILITY AND OTHER PHARMACOKINETIC PARAMETERS OF NALTREXONE IN MAN AFTER ACUTE AND CHRONIC ORAL-ADMINISTRATION

Abstract

First pass metabolism, metabolic clearance, volume of distribution and steady state plasma levels were estimated in man following acute and chronic 100 mg oral doses of naltrexone. Essentially no statistical difference was observed in these values between the acute and chronic physiologic state. The values for the 1st pass effect were 79.6 .+-. 4.6% and 78.0 .+-. 3.0% for acute and chronic treatment, respectively. An apparent chronic release rate (ACRR) for a sustained release preparation of naltrexone was calculated at 11.8 .mu.g/kg per h. In practice a release rate of 1/2 the ACRR should sufficiently provide continuous antagonism of 25 mg i.v. heroin. Naltrexone apparently is an effective and safe narcotic antagonist in man.