[Pharmacokinetics of naltrexone hydrochloride and naltrexone glucuronide in the dog]

Pharmacokinetics of naltrexone hydrochloride (NTX) and naltrexone glucuronide was studied in the dog using HPLC-electrochemical detection with naloxone as internal standard. After iv 5 mg or po 10 mg NTX, the plasma concentration-time curves of NTX were found to fit to a two-compartment model and a single compartment with first-order absorption. The elimination half-lives of NTX were 78 +/- 6 min and 74 +/- 6 min, respectively. Although NTX could be absorbed rapidly in the dog after po administration, the plasma concentration of the parent drug was very low and its absolute bioavailability was 15.8%. The experiments showed that the major metabolite of NTX in dog plasma was beta-glucuronidase-hydrolyzable conjugate. Dosing NTX intravenously and orally, the plasma levels of the conjugate were 1.3 and 23 times as high as that of the parent drug, the elimination half-lives of the glucuronide from plasma were 3.4 h and 12.6 h, respectively. The results indicate that NTX is subjected to a marked first-pass effect in the dog after oral administration.