盐酸纳曲酮片剂在正常人体的药代动力学及相对生物利用度

PHARMACOKINETICS AND RELATIVE BIOAVAILABILITY OF NALTREXONE HYDROCHLORIDE TABLET IN CHINESE HEALTHY VOLUNTEERS BY HPLC

在中国男性健康自愿者体内进行了国产盐酸纳曲酮片剂与进口盐酸纳曲酮片剂的相对生物利用度试验。１０名健康自愿者随机自身交叉服用５０ｍｇ国产盐酸纳曲酮片和进口盐酸纳曲酮片，应用高效液相色谱－电化学检测器测定盐酸纳曲酮及其主要代谢产物纳曲醇的血浆浓度。盐酸纳曲酮两种片剂在健康人体内的血药浓度－时间过程符合一级吸收二室模型。国产盐酸纳曲酮片剂的药代动力学参数分别为：Ｔ１／２β２．９７±０．６１ｈ，Ｔｐｅａｋ０．８１±０．０９ｈ，Ｃｍａｘ１７．２±２．６μｇ／Ｌ，ＡＵＣ６４．７±９．４μｇ．ｈ·Ｌ－１。进口盐酸纳曲酮片的药代动力学参数分别为：Ｔ１／２β３．３４±１．４９ｈ，Ｔｐｅａｋ１．０９±０．２５ｈ，Ｃｍａｘ１６．６±１．６μｇ·Ｌ－１，ＡＵＣ６６．２±８．４μｇ·ｈ·Ｌ－１。除了Ｔｐｅａｋ和Ｔ１／２α国产片稍快于进口片外，两种片剂的Ｔ１／２β、Ｃｍａｘ、ＡＵＣ等主要药代动力学参数之间经统计学检验均无显著性差异（Ｐ＞０．０５），国产与进口盐酸纳曲酮片剂的相对生物利用度为９８．６±１４％。口服国产和进口两种盐酸纳曲酮片剂后，血浆中主要代谢产物纳曲醇的药代动力学参数无显著性差异，Ｔ１／２β分别为９．９±１．８和７．６±?

The Pharmacokinetics and relative bioavailability of naltrexone hydrochloride (NTX) tablet was measured in Chinese healthy volunteers. A single 50 mg oral doses of domestic NTX tablet (Institute of Pharmacology and Toxicology) or imported tablet (TREXANR,Du PontPharmaceutical Corporation) was given to 10 healthy male volunteers in randomized self-crossover study.Plasma samples were taken in the different time after admindistration of the tablets.The parent drug and its major metabolite, naltrexol (NOL) were extracted with a mixed solvent of benzene-ethanol from plasma,then detected by high performance liquid chromatograph with electrochemical detector.Two-compartment model with first-order absorption was fitted to the NTX concentration-time curves following oral administration of the two tablets. The pharmacokinetic parameters obtained by nonlinear least squares estimation for each individual subject. Pharmacokinetic parameters for domestic NTX tablet were T1/2β 2.69±0.61 h, Tpeak 0.81±0.09 h, Cmax 17.2±2.6 μg·L-1, AUC 64.7±9.4 μg·h·L-1, respectively; for TREXANR were T1/2β 3.34±1.49 h, Tpeak 1.09±0.25 h, Cmax 16.6±1.6 μg·L-1, AUC 66.2±8.4 μg·h·L-1, respectively. The statistic test showed that these pharmacokinetic parameters were not significantly different between the two kinds of tablets except Tpeak and T1/2α.Relative bioavailability of domestic tablet was 98.6±14% compared with TREXANR in Chinese male volunteers. The pharmacokinetic parameters of NOL for domestic and TREXANR were 9.9±1.8 and 7.6±1.4 h of T1/2 β, 0.67±0.13 and 0.86±0.22 h of Tpeak, 38.7±7.6 and 36.5±5.8 μg·L-1 of Cmax, 270.2±52.2 and 255.4±39.5 μg·h·L-1 of AUC.