在异喹胍（细胞色素P450 2D6）和美芬妥英（细胞色素P450 2C19）的广泛代谢者和代谢不良者中，氯沙坦转化为其活性代谢物E-3174缺乏多态性。
Lack of polymorphism of the conversion of losartan to its active metabolite E-3174 in extensive and poor metabolizers of debrisoquine (cytochrome P450 2D6) and mephenytoin (cytochrome P450 2C19).
作者信息
Sandwall P, Lo M W, Jonzon B, Dalén P, Furtek C, Ritter M, Alván G, McCrea J, Sjöqvist F
机构信息
Department of Clinical Research, Merck Sharp & Dohme (Sweden) AB, Sollentuna.
出版信息
Eur J Clin Pharmacol. 1999 Jun;55(4):279-83. doi: 10.1007/s002280050629.
OBJECTIVE
Losartan was given to subjects with known phenotypes of the polymorphic enzymes CYP2D6 and CYP2C19 to study any possible influence on the metabolism of the drug.
METHODS
Plasma concentrations of losartan and E-3174 were studied after oral intake of 50 mg losartan in 24 healthy, male, Swedish Caucasian subjects who were extensive or poor metabolizers (EM/PM) of debrisoquine [cytochrome P450 2D6 (CYP2D6)] or mephenytoin [cytochrome P450 2C19 (CYP2C19)].
RESULTS
The areas under the curve (AUCinfinity) of losartan and E-3174 did not differ between poor and extensive metabolizers of debrisoquine or mephenytoin, respectively.
CONCLUSION
About 14% of the antihypertensive drug losartan is metabolized to the active carboxylic acid metabolite E-3174, which contributes to the effect of losartan. The present study suggests that CYP2D6 and CYP2C19 are not involved to any major extent in the in vivo conversion of losartan to E-3174.
目的
给予已知具有多态性酶CYP2D6和CYP2C19表型的受试者氯沙坦，以研究其对该药物代谢的任何可能影响。
方法
在24名健康、男性、瑞典高加索受试者口服50mg氯沙坦后，研究氯沙坦和E - 3174的血浆浓度。这些受试者分别是异喹胍[细胞色素P450 2D6（CYP2D6）]或美芬妥因[细胞色素P450 2C19（CYP2C19）]的快代谢型或慢代谢型。
结果
氯沙坦和E - 3174的曲线下面积（AUC∞）在异喹胍或美芬妥因的慢代谢型和快代谢型受试者之间分别无差异。
结论
约14%的抗高血压药物氯沙坦被代谢为活性羧酸代谢物E - 3174，这对氯沙坦的疗效有贡献。本研究表明，CYP2D6和CYP2C19在很大程度上不参与氯沙坦在体内向E - 3174的转化。
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