Abstract
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 (AUC∞) 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.
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Received: 21 April 1998 / Accepted in revised form: 16 December 1998
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Sandwall, P., Lo, MW., Jonzon, B. et al. 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). E J Clin Pharmacol 55, 279–283 (1999). https://doi.org/10.1007/s002280050629
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DOI: https://doi.org/10.1007/s002280050629