Inhibitory effect of ketoconazole and voriconazole on the pharmacokinetics of carvedilol in rats |
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| Authors: | Li Wang Shuanghu Wang Mengchun Chen Xinxin Chen Yuxian Lin Xiaoxia Hu |
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| Affiliation: | 1. Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China and;2. The Laboratory of Clinical Pharmacy, The People’s Hospital of Lishui, Lishui, Zhejiang, China |
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| Abstract: | The aim of this study was to investigate the effect of orally administered ketoconazole and voriconazole on the pharmacokinetics of carvedilol and its metabolites in rats. Fifteen healthy male Sprague–Dawley (SD) rats were randomly divided into three groups: A group (30?mg/kg ketoconazole), B group (30?mg/kg voriconazole) and C group (control group). A single dose of carvedilol was administered orally 30?min after administration of ketoconazole and voriconazole. Carvedilol and its metabolites plasma levels were measured by ultra-high performance liquid chromatography-mass spectrometry method (UPLC–MS/MS), and pharmacokinetic parameters were calculated by DAS 3.0 software. The co-administrated with ketoconazole could significantly increase the maximal plasma concentration (Cmax) and area under the curve (AUC) of carvedilol (p?Cmax of its three metabolites 4′-hydroxyphenyl carvedilol (4′-HPC), 5′-hydroxyphenyl carvedilol (5′-HPC) and o-desmethyl carvedilol (o-DMC) decreased drastically by 39.4% (p?p?p?Tmax of carvedilol and o-DMC increased, and the Cmax of 5′-HPC decreased by 27.7% (p?
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| Keywords: | Carvedilol cytochrome P450 inhibitory effect ketoconazole pharmacokinetics voriconazole |
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