Estimation of the systemic availability and other pharmacokinetic parameters of naltrexone in man after acute and chronic oral administration.

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 differences was observed in these values between the acute and chronic physiologic state. The values for the first pass effect were 79.6 +/- 4.6% and 78.0 +/- 3.0% for acute and chronic treatment respectively. From our pharmacokinetic data an apparent chronic release rate (ACRR) for a sustained release preparation of naltrexone was calculated as 11.8 microgram/kg/hr. In practice a release rate of one half the ACRR should be sufficient to provide continuous antagonism of 25 mg i.v. heroin. In conclusion our data clearly indicate that naltrexone is an effective and safe narcotic antagonist in man.