High Performance Liquid Chromatography Using UV Detection for the Simultaneous Quantification of the New Non-nucleoside Reverse Transcriptase Inhibitor Etravirine (TMC-125), and 4 Protease Inhibitors in Human Plasma
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概要
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Etravirine (TMC-125, ETV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that demonstrates potent activity against NNRTI-resistant strains of human immunodeficiency virus type-1 (HIV-1). Thus, ETV has been used in combination with ritonavir-boosted protease inhibitor (PI) and integrase inhibitor for therapy-experienced HIV-1-infected patients. On the other hand, as ETV is a substrate and inducer of cytochrome P450 3A4 (CYP3A4), ETV may induce metabolism of PI and alter the concentrations of co-administered PIs. In order to ensure optimal drug efficacy and prevention of resistance, it is essential to monitor plasma concentrations of ETV and PIs. Here we describe the application of HPLC with UV detection for the simulataneous assay of ETV and 4 PIs, darunavir (DRV), atazanavir (ATV), ritonavir (RTV) and lopinavir (LPV). In this study, the calibration curve of each drug was linear with the average accuracy ranging from 93.6 to 110.9%. Both intra- and interday coefficients of variation for each drug were less than 11.6%. The mean recovery of all drugs ranged from 88.0 to 97.5%. The limit of quantification was 0.04, 0.04, 0.04, 0.05 and 0.07 μg/ml for ETV, DRV, ATV, RTV and LPV, respectively. These results demonstrate that our HPLC-UV method can be used for routine determination of plasma concentrations of ETV and 4 PIs in clinical settings.
著者
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SHIBATA Masaaki
Department of Electrical and Mechanical Engineering, Seikei University
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Hamaguchi Motohiro
Clinical Res. Center National Hospital Organization Nagoya Medical Center
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Hirano Atsushi
Department of Pharmacy, National Hospital Organization Nagoya Medical Center
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Takahashi Masaaki
Department of Pharmacy, National Hospital Organization Nagoya Medical Center
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Kinoshita Eri
Department of Pharmacy, National Hospital Organization Nagoya Medical Center
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Nomura Toshiharu
Department of Pharmacy, National Hospital Organization Nagoya Medical Center
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Yokomaku Yoshiyuki
Clinical Research Center, National Hospital Organization Nagoya Medical Center
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Sugiura Wataru
Clinical Research Center, National Hospital Organization Nagoya Medical Center
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Sugiura Wataru
Clinical Res. Center National Hospital Organization Nagoya Medical Center
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Yokomaku Yoshiyuki
Clinical Res. Center National Hospital Organization Nagoya Medical Center
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Hirano Atsushi
Department Of Pharmacy National Hospital Organization Nagoya Medical Center (tokai Area Central Hosp
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Shibata Masaaki
Department Of Applied Chemistry & Biochemistry Faculty Of Engineering Kumamoto University
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Takahashi Masaaki
Department Of Applied Biological Sciences Graduate School Of Life And Environmental Sciences Osaka P
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Hirano Atsushi
Department Of Applied Chemistry And Chemical Engineering Kagoshima Univ
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Takahashi Masaaki
Department Of Applied Biological Chemistry Faculty Of Agriculture Osaka Prefecture University
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Shibata Masaaki
Department of Pharmacy, National Hospital Organization Nagoya Medical Center
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Hamaguchi Motohiro
Clinical Research Center, National Hospital Organization Nagoya Medical Center
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