Abstract: Pharmacokinetics of naltrexone hydrochloride(NTX)and naltrexone glucuronidewas studied in the dog using HPLC-electrochemical detection with naloxone as internal standard.Aftetiv 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 firstorder absorption,The elimination half-livesof NTX were 78±6　min and 74±6min,respectively.Although NTX could be absorbed rapidly inthe dog after po administration,the plasma concentration of the parent drug was very low and itsabolute bioavailability was 15.8%,The experiments showed that the major metabolite of NTX indog plasma was β-glucuronidase- hydrolyzable conjugate. Dosing NTX intravenously and orally,theplasma levels of the conjugate were 1.3 and 23 times as high as that of the parent drug,theelimination half lives of the glucuronide from plasma were 3.4 h and 12.6h,respectively.Theresults indicate that NTX is subjected to a marked first-pass effect in the dog after oral administration.