Inhibitory Effects on Cytochrome P450 Enzymes of Pentamidine and Its Amidoxime Pro-Drug
Anja Bürenheide,
Thomas Kunze,
Bernd Clement,
Anja Bürenheide
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorThomas Kunze
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorBernd Clement
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorAnja Bürenheide,
Thomas Kunze,
Bernd Clement,
Anja Bürenheide
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorThomas Kunze
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorBernd Clement
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany
Search for more papers by this authorAuthor for correspondence: Bernd Clement, Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, D-24118 Kiel, Germany (fax 049-(0)431-880 1352, e-mail [email protected]).
Abstract
Abstract: Pentamidine is an antimicrobial drug, intravenously used in the treatment of trypanosomiasis, leishmaniasis or pneumocystis pneumonia. To elucidate potential drug interactions with pentamidine and N,N′-dihydroxypentamidine, respectively, the cytochrome P450 (CYP450) inhibitory properties of these compounds were determined. The study was performed in vitro by using human liver microsomes and marker substrates of several CYP450 isoenzymes. Marker activities were investigated by high-performance liquid chromatography in presence of known selective inhibitors or at different concentrations of pentamidine and N,N′-dihydroxypentamidine, respectively. No or only minor influence on CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 marker activities could be observed, suggesting that neither of the tested substances would exert a significant effect on hepatic CYP450 isoenzymes responsible for the metabolism of co-administrated drugs in vivo. However, in vivo studies are needed before final conclusions can be drawn.
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