Effects of the combination of ketoconazole and calcium channel antagonists against Candida albicans in vitro

Abstract

Susceptibility of 66 strains of Candida albicans from patients were tested against ketoconazole (Ktz, CAS 65277-42-1), cinnarizine (Cin), verapamil (Ver), nifedipine (Nif), nimodipine (Nim) and the combination of Ktz with these calcium channel antagonists, using Sabouraud's broth. Minimal inhibitory concentrations (MICs) determined on diagnostic plates gave values of Ktz: 34.5 +/- 3.9 micrograms/ml, Cin 413 +/- 11.3 micrograms/ml, Ver 334 +/- 11.4 micrograms/ml, Nif 374 +/- 19.3 micrograms/ml and Nim 486 +/- 20 micrograms/ml. The combination of Ktz and calcium channel antagonists in various ratios (1 : 1, 1 : 2, 2 : 1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Cin 6.52 +/- 1.67, 6.4 +/- 1.71, 6.06 +/- 1.7 micrograms/ml: Ktz+Ver 11.13 +/- 2.13, 11.63 +/- 2.22, 10.6 +/- 2.1 micrograms/ml: Ktz+Nif 7.37 +/- 1.6, 7.7 +/- 1.57, 7.4 +/- 1.75 micrograms/ml: Ktz+Nim 10.1 +/- 2.28, 10.6 +/- 2.31, 9.91 +/- 2.21 micrograms/ml. These results were significantly different (p < 0.001) compared with ketoconazole. Our findings indicate that some calcium channel antagonists increase the antifungal activity of Ktz against C. albicans in vitro.