Efficacy of parenteral itraconazole against disseminated Candida albicans infection in two mouse strains.
The efficacy of a new cyclodextrin intravenous formulation of itraconazole was evaluated by intraperitoneal treatment of experimental disseminated Candida albicans infections in BALB/c and DBA/2 mice. Mice were treated with doses of 5 or 20 mg/kg for 14 days and observation was continued for 28 days. Mice were randomly assigned to groups given either water or grapefruit juice as drinking fluid, since components of grapefruit juice that inhibit cytochrome P450 enzymes might influence the pharmacokinetic behaviour of itraconazole. The experiments showed that the itraconazole/cyclodextrin solution unequivocally prolonged survival and reduced weight loss over the first 4 days post-challenge, relative to placebo-treated control animals, in both mouse strains. However, the antifungal treatments did not reduce burdens of C. albicans in kidneys or brain. Placebo-treated DBA/2 mice given grapefruit juice to drink had a significantly shorter mean survival time than the equivalent group given water. In BALB/c mice the placebo-treated animals given grapefruit juice survived longer, though not significantly longer, than placebo-treated animals given water. These results give a preliminary hint that grapefruit juice alters the susceptibility of some mouse strains to C. albicans infection, regardless of any effects or non-effects it may have on itraconazole pharmacokinetics in the animals.
MacCallum
Donna M
DM
Department of Molecular and Cell Biology, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK.
Odds
Frank C
FC
D000818:Animals; D001628:Beverages; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D032083:Citrus paradisi; D005260:Female; D007263:Infusions, Parenteral; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013045:Species Specificity; D016019:Survival Analysis
D017964:Itraconazole