title: High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes.
abstract: Fisher rat liver microsomes metabolized the antimicrobial drug pentamidine to four new compounds detected by gradient elution reversed-phase high-performance liquid chromatography with variable wavelength detection. Coelution experiments with pentamidine metabolite standards determined the new peaks to be previously identified hydroxylated metabolites of pentamidine, with 1,5-bis(4'-amidinophenoxy)-3-pentanol and 1,5-di-(4'-amidinophenoxy)-2-pentanol formed in the greatest amount. The data contradict a previous report that Fisher rat liver homogenates do not metabolize pentamidine. Pentamidine and its known primary metabolites have almost identical absorption spectra; thus, pentamidine metabolism must be evaluated using gradient elution HPLC to resolve pentamidine from its metabolites. The current assay has now been used to demonstrate that Fisher and Sprague-Dawley rat, mouse, rabbit and human liver microsomes all metabolize pentamidine in vitro.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill 27599-7525, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Tuttle
authors.forename: J E
authors.initials: JE
authors.lastname: Hall
authors.forename: R R
authors.initials: RR
authors.lastname: Tidwell
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010419:Pentamidine / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000981:Antiprotozoal Agents; D010419:Pentamidine