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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 406 - 414 (9page)
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Background: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19 influence voriconazole pharmacokinetics. However,the impact of CYP2C19 genetic polymorphisms on the therapeutic efficacy and toxicity of voriconazole therapy are not well established.
Materials and Methods: In this prospective observational study, we analyzed all consecutive adult patients with hematologic diseaseswho were treated for invasive aspergillosis (IA) with voriconazole between January 2011 and June 2012. CYP2C19 genotype androutine therapeutic drug monitoring of voriconazole were performed. The target range for voriconazole trough levels was 1−5.5 mg/L.
Results: A total of 104 consecutive patients were enrolled, including 39 homozygous extensive metabolizers (EMs, 38%), 50 heterozygousextensive metabolizers (HEMs, 48%), and 15 poor metabolizers (PMs, 14%). The initial voriconazole trough levels were 1.8, 2.7, and 3.2mg/L in EMs, HEMs, and PMs, respectively (P = 0.068). Out-of-range initial trough levels were most frequently observed in EMs (46%) followedby HEMs (26%) and PMs (0%) (P = 0.001). The frequency of initial trough levels < 1 mg/L but not > 5.5 mg/L differed significantlyamong the 3 groups (P = 0.005). However, treatment response, all-cause and IA-attributable mortality, and the occurrence of voriconazolerelatedadverse events did not differ significantly among the 3 groups (P = 0.399, P = 0.412, P = 0.317, and P = 0.518, respectively).
Conclusions: While none of the initial voriconazole trough levels in PMs was outside the target range, subtherapeutic initialtrough levels were frequent in EMs. Although there was no significant relationship between CYP2C19 genotype and either theclinical outcomes of IA or toxicity of voriconazole, further large-scale multicenter studies using clinical data from homogeneouspopulations are required.
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참고문헌 (21)
참고문헌 신청
Andes D / 2009 / Antifungal therapeuticdrug monitoring: established and emerging indications / Antimicrob Agents Chemother 53 : 24 ~ 34
Baldwin RM / 2008 / Ingelman-Sundberg M, Eliasson E, Bertilsson L. Increased omeprazolemetabolism in carriers of the CYP2C19*17 allele; apharmacokinetic study in healthy vol
Berge M / 2011 / Effect of cytochromeP450 2C19 genotype on voriconazole exposure incystic fibrosis lung transplant patients / Eur J Clin Pharmacol 67 : 253 ~ 260
Bruggemann RJ / 2008 / Therapeuticdrug monitoring of voriconazole / Ther Drug Monit 30 : 403 ~ 411
De Pauw B / 2008 / European Organizationfor Research and Treatment of Cancer/Invasive FungalInfections Cooperative Group; National Institute of Allergyand Infectious Disease
Baldwin RM / 2008 / Ingelman-Sundberg M, Eliasson E, Bertilsson L. Increased omeprazolemetabolism in carriers of the CYP2C19*17 allele; apharmacokinetic study in healthy vol
Berge M / 2011 / Effect of cytochromeP450 2C19 genotype on voriconazole exposure incystic fibrosis lung transplant patients / Eur J Clin Pharmacol 67 : 253 ~ 260
Bruggemann RJ / 2008 / Therapeuticdrug monitoring of voriconazole / Ther Drug Monit 30 : 403 ~ 411
De Pauw B / 2008 / European Organizationfor Research and Treatment of Cancer/Invasive FungalInfections Cooperative Group; National Institute of Allergyand Infectious Disease
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