[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.
Li
H
H
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing.
Zhao
S F
SF
Wang
N
N
Ge
Z H
ZH
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D004563:Electrochemistry; D008297:Male; D009271:Naltrexone / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000493:pharmacokinetics*
D009292:Narcotic Antagonists; D009271:Naltrexone