Evaluation of amphotericin B-cyclosporine interaction in the rat.
Although a significant interaction between cyclosporine and amphotericin-B (AmpB) has been observed clinically, these findings have not been duplicated in animal studies. A total of 64 male albino rats were used in single- and multiple-dose experiments with AmpB and CsA in the absence or presence of systemic Candida infection. No significant differences in glomerular filtration rate were found in rats given single i.v. doses of AmpB 1 mg/kg compared with AmpB and CsA. Furthermore, rats given i.p. AmpB 1 mg/kg and CsA 10 mg/kg daily for 10 days showed no significant differences in GFR compared with animals given CsA alone. Morphology and CsA whole-blood pharmacokinetics were not different between groups administered single-dose CsA, AmpB, or the combination; similarities also existed with multiple-dose studies. In an attempt to mimic the clinical setting, 2 groups of rats were administered i.p. CsA 10 mg/kg/day for 10 days followed by inoculation of Candida albicans. After 48 hr, a single i.v. dose of AmpB 1.0 mg/kg was associated with a 33% decline in GFR compared with those given sterile water (P less than 0.05). Systemic clearance of CsA was markedly reduced in candidiasis rats administered AmpB compared with controls given sterile water. A significant reduction in renal Candida colony-forming units was found in rats given CsA and AmpB compared with those administered CsA alone. These data suggest that the presence of systemic Candida highlights the interaction of CsA and AmpB in the rat model.
Department of Pharmaceutics, University of Houston, Texas.
J D
JD
Langston
K M
KM
Wasan
G
G
Lopez-Berestein
R R
RR
Verani
D R
DR
Luke
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002176:Candida albicans; D002177:Candidiasis; D003524:Cyclosporins / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D000666:Amphotericin B