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拉米夫定在大鼠体内的临床前药代动力学及其与提取物的相互作用。

Preclinical Pharmacokinetics of Lamivudine and Its Interaction with Extract in Rats.

作者信息

Li Chi-Lin, Hsieh Chen-Hsi, Tsai Tung-Hu

机构信息

Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.

Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei 220, Taiwan.

出版信息

ACS Omega. 2020 Jan 22;5(4):1997-2004. doi: 10.1021/acsomega.9b03922. eCollection 2020 Feb 4.

Abstract

(Turcz.) Baill. () extract and its active ingredient, schizandrin, have been used as a botanical medicine and dietary supplement for the treatment of hepatitis. Lamivudine is an antiretroviral drug and is used to treat hepatitis B viral infection. The aim of this study was to develop an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the measurement of lamivudine and to determine the pharmacokinetic behaviors of an aqueous-ethanol extract of in rats. The separation was performed on a phenyl column maintained at 40 °C. The experimental animals were distributed into three groups: (1) lamivudine alone (10 mg/kg, i.v.); (2) lamivudine (10 mg/kg, i.v.) + pretreatment with (3 g/kg, p.o.); and (3) lamivudine (10 mg/kg, i.v.) + pretreatment with (10 g/kg, p.o.). The experimental results indicated that neither treatment with lamivudine alone nor pretreatment with (3 or 10 g/kg) significantly changed the pharmacokinetic parameters. In conclusion, based on the above preclinical experimental model, the combination of lamivudine with the herbal extract of did not exhibit significant pharmacokinetic interactions. These data offer useful information for assessing the preclinical safety of nutritional supplementation with lamivudine.

摘要

(Turcz.)Baill.()提取物及其活性成分五味子醇甲已被用作治疗肝炎的植物药和膳食补充剂。拉米夫定是一种抗逆转录病毒药物,用于治疗乙型肝炎病毒感染。本研究的目的是开发一种超高效液相色谱-串联质谱(UHPLC-MS/MS)方法来测定拉米夫定,并确定大鼠中()水-乙醇提取物的药代动力学行为。分离在40℃的苯基柱上进行。实验动物分为三组:(1)单独使用拉米夫定(10mg/kg,静脉注射);(2)拉米夫定(10mg/kg,静脉注射)+()预处理(3g/kg,口服);(3)拉米夫定(10mg/kg,静脉注射)+()预处理(10g/kg,口服)。实验结果表明,单独使用拉米夫定治疗或()(3或10g/kg)预处理均未显著改变药代动力学参数。总之,基于上述临床前实验模型,拉米夫定与()草药提取物联合使用未表现出显著的药代动力学相互作用。这些数据为评估拉米夫定营养补充剂的临床前安全性提供了有用信息。

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