In:
The Journal of Clinical Pharmacology, Wiley, Vol. 39, No. 4 ( 1999-04), p. 418-424
Abstract:
Losartan is an angiotensin II receptor antagonist that is metabolized by CYP2C9 and CYP3A4 to a more potent antihypertensive metabolite, E3174. Interaction studies with inhibitors of CYP3A4 have not demonstrated significant changes in the pharmacokinetics of losartan or E3174. The authors assessed the steady‐state pharmacokinetics of losartan and E3174 when administered alone and concomitantly with fluvastatin, a specific CYP2C9 inhibitor. A prospective, open‐label, crossover study was conducted in 12 healthy volunteers with losartan alone and in combination with fluvastatin. The baseline phase was 7 days of losartan (50 mg QAM), and the inhibition phase was 14 total days of fluvastatin (40 mg QHS), with the final 7 days including losartan. The authors found that flvastatin did not significantly change the steady‐state AUC 0–24 or half‐life of losartan or E3174. Losartan apparent oral clearance was not affected by fluvastatin. Inhibition of losartan metabolism appears to require both CYP2C9 and CYP3A4 inhibition .
Type of Medium:
Online Resource
ISSN:
0091-2700
,
1552-4604
DOI:
10.1177/00912709922007886
Language:
English
Publisher:
Wiley
Publication Date:
1999
detail.hit.zdb_id:
2010253-7
SSG:
15,3
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