title: Inhibitory effects on cytochrome p450 enzymes of pentamidine and its amidoxime pro-drug.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bürenheide
authors.forename: Thomas
authors.initials: T
authors.lastname: Kunze
authors.forename: Bernd
authors.initials: B
authors.lastname: Clement
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D011355:Prodrugs; C066942:N,N'-dihydroxypentamidine; D010419:Pentamidine; D003577:Cytochrome P-450 Enzyme System