caa a22 4500 475818377 CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s002280000125 doi (NATIONALLICENCE)springer-10.1007/s002280000125 Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole [Elektronische Daten] [L. L. von Moltke, A. L. B. Durol, S. X. Duan, D. J. Greenblatt] Objective: Biotransformation of triazolam to its α-hydroxy and 4-hydroxy metabolites by human liver microsomes in vitro was used as an index of human cytochrome P 450 3A (CYP3A) activity. Results: The reaction was strongly inhibited by co-incubation with the viral protease inhibitors ritonavir (IC50=0.14 μM) and amprenavir (IC50=2.5-2.9 μM), and by the azole derivative ketoconazole (IC50 = 0.07 μM). Pre-incubation of microsomes with ritonavir or amprenavir increased inhibitory potency (IC50 reduced to 0.07 μM and 1.4 μM, respectively). This was not the case with ketoconazole. Conclusions: Thus, ritonavir and amprenavir are highly potent mechanism-based inhibitors of human CYP3A isoforms. Springer-Verlag Berlin Heidelberg, 2000 Key words Human CYP3A nationallicence Amprenavir nationallicence Ritonavir nationallicence von Moltke L. L. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut Durol A. L. B. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut Duan S. X. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut Greenblatt D. J. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut https://doi.org/10.1007/s002280000125 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000125 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- von Moltke L. L. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut NATIONALLICENCE 700 1- Durol A. L. B. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut NATIONALLICENCE 700 1- Duan S. X. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut NATIONALLICENCE 700 1- Greenblatt D. J. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: Lisa.vonmoltke@tufts.edu Tel.: +1-617-6366997; Fax: +1-617-6366738, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer