title: The activity of protease inhibitors against Giardia duodenalis and metronidazole-resistant Trichomonas vaginalis.
abstract: Antiretroviral protease inhibitors were assessed in vitro for their activity against Giardia duodenalis and Trichomonas vaginalis. Kaletra (a co-formulation of ritonavir and lopinavir) was the most effective overall, with 50% effective drug concentrations (EC(50)) of 1.1-2.7 microM (ritonavir concentration) against G. duodenalis and 6.8-8 microM against metronidazole-sensitive and clinically metronidazole-resistant T. vaginalis. Minimal inhibitory concentrations were 2-2.5 microM and 10-50 microM for G. duodenalis and T. vaginalis, respectively. Within the range of human plasma concentrations for ritonavir, only G. duodenalis was inhibited. Lopinavir alone was less inhibitory than ritonavir but was associated with a blockage in cytokinesis of G. duodenalis trophozoites. Saquinavir was not effective. These findings are significant considering the association between human immunodeficiency virus and T. vaginalis, and between G. duodenalis and homosexual behaviour.
authors.affiliation: Molecular Genetics Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Qld 4006, Australia. Linda.Dunn@qimr.edu.au
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dunn
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Andrews
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Wright
authors.forename: Tina S
authors.initials: TS
authors.lastname: Skinner-Adams
authors.forename: Peter
authors.initials: P
authors.lastname: Upcroft
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Upcroft
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D048749:Cytokinesis / Q000187:drug effects; D004351:Drug Resistance; D016829:Giardia lamblia / Q000166:cytology / Q000187:drug effects* / Q000302:isolation & purification; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D061466:Lopinavir; D008795:Metronidazole / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000981:Antiprotozoal Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D008795:Metronidazole; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir