Preclinical Pharmacokinetics of Lamivudine and Its Interaction with Schisandra chinensis Extract in Rats

拉米夫定在大鼠体内的临床前药代动力学及其与五味子提取物的相互作用

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Abstract

Schisandra chinensis (Turcz.) Baill. (S. chinensis) 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 S. chinensis 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 S. chinensis (3 g/kg, p.o.); and (3) lamivudine (10 mg/kg, i.v.) + pretreatment with S. chinensis (10 g/kg, p.o.). The experimental results indicated that neither treatment with lamivudine alone nor pretreatment with S. chinensis (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 S. chinensis did not exhibit significant pharmacokinetic interactions. These data offer useful information for assessing the preclinical safety of nutritional supplementation with lamivudine.

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