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Inhibitory Effects on Cytochrome P450 Enzymes of Pentamidine and Its Amidoxime Pro‐Drug
Author(s) -
Bürenheide Anja,
Kunze Thomas,
Clement Bernd
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00236.x
Subject(s) - pentamidine , in vivo , pharmacology , cyp1a2 , microsome , drug , cytochrome p450 , chemistry , didanosine , drug metabolism , enzyme , in vitro , cyp2d6 , pharmacokinetics , biochemistry , biology , medicine , pneumonia , human immunodeficiency virus (hiv) , immunology , microbiology and biotechnology , antiretroviral therapy , viral load
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.