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Effect of atorvastatin on CYP2C9 metabolic activity in hypercholesterolemic patients
Author(s) -
Babaoglu Melih O.,
Yasar Umit,
Yardimci Yildiz,
Kilicaslan Alpaslan,
SainGuven Gulay,
Bozkurt Atila
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1185-c
Clinical reports suggest that HMG‐CoA reductase inhibitors (statins) may interact with substrates of drug metabolizing enzyme CYP2C9. We investigated if this interaction was due to the inhibition of CYP2C9 by statins. Hypercholesterolemic Turkish patients (13 women, 7 men) that used atorvastatin participated into the study. Losartan was used as a probe drug to determine CYP2C9 metabolic activity. A single 25 mg oral dose of losartan was given to the patients before, on the first day and after the fourth week of atorvastatin treatment. Urinary concentrations of losartan and its metabolite E3174 were measured by high‐pressure liquid chromatography. CYP2C9∗2 and ∗3 alleles were identified by using PCR‐RFLP. Losartan/E3174 ratios (median, range) were used to predict CYP2C9 activity. Atorvastatin treatment did not cause a significant change in losartan/E3174 ratio either on the first day (0.81, 0.23 – 3.85) or at the fourth week of the treatment (0.58, 0.19 – 4.26) as compared to the baseline (0.84, 0.23 – 3.78; P=0.66). The change in the metabolic ratio was also not evident in patients with the different genotypes for CYP2C9 ( ∗1/∗1 , n=13; ∗1/∗2 , n=4; ∗1/∗3 , n=3). These results suggest that atorvastatin treatment does not have a significant effect on CYP2C9 activity. (Supported by TUBITAK‐SBAG COST B25‐105S027 and UY/TUBA‐GEBIP/2005‐17)