کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3360040 1591847 2009 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes
چکیده انگلیسی

Voriconazole metabolism is mostly mediated via the cytochrome P450 (CYP) 2C19 isozyme. The non-wild (mutant) type of CYP2C19 is generally found in 60–70% of Asian populations. Because the voriconazole trough plasma concentration has been reported to correlate with hepatotoxicity, this study investigated the effect of CYP2C19 polymorphism on the relationship between voriconazole trough concentrations and liver function abnormalities in 29 Japanese patients with fungal infections (CYP2C19 wild-type, n = 10; non-wild-type, n = 19). Hepatotoxicity, defined as liver enzyme abnormality according to the National Cancer Institute criteria, was observed in 10 (34.5%) of 29 patients with a trough concentration ≥3.9 mg/L. Logistic regression analysis suggested that the therapeutic range for the voriconazole trough concentration should be 2–4 mg/L. Non-linear pharmacokinetic analysis suggested that voriconazole therapy should be initiated with a dose of 7.2–8.9 mg/kg/day for CYP2C19 wild-type and 4.4–6.5 mg/kg/day for the non-wild-type in Japanese patients. These recommended initial dosages and subsequent dose adjustment for the target concentration range by therapeutic drug monitoring should avoid adverse events and thus enable continued effective voriconazole therapy for Japanese patients with mycoses.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 34, Issue 1, July 2009, Pages 91–94
نویسندگان
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