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).

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 (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.

journal_name

Eur J Clin Pharmacol

authors

Sandwall P,Lo MW,Jonzon B,Dalén P,Furtek C,Ritter M,Alván G,McCrea J,Sjöqvist F

doi

10.1007/s002280050629

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

279-83

issue

4

eissn

0031-6970

issn

1432-1041

journal_volume

55

pub_type

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