盐酸纳曲酮及其葡萄糖醛酸结合物在犬体内的药代动力学

用高效液相色谱-电化学检测法测定了盐酸纳曲酮(NTX)在犬体内的药代动力学。犬iv和poNTX的血浆药。时曲线分别符合二室模型和一级吸收一室模型,消除半衰期分别为78±6min和74±6min。犬po　NTX吸收较快,但血中原形药物浓度较低,绝对生物利用度为15.8%。NTX经iv和po两种途径给药后血浆中的主要代谢产物为NTX的葡萄糖醛酸苷,其血浆浓度分别为NTX的1.3和23倍,未端相消除半衰期分别为3.4h和12.6h。

PHAKMACOKINETICS OF NALTREXONE HYDROCHLORIDE AND NALTKEXONE GLUCURONIDE IN THE DOG

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.