Pharmacokinetic study of azithromycin with fluconazole and cotrimoxazole (trimethoprim-sulfamethoxazole) in healthy volunteers

Background: Azithromycin, fluconazole and cotrimoxazole (trimethoprim-sulfamethoxazole; TMP/SMX) are all agents that are utilised for the treatment and/or prophylaxis of opportunistic infections in patients with AIDS. Objective: To characterise the potential for an interaction when azithromycin is coadministered with cotrimoxazole or with fluconazole. Design: Two separate nonblind randomised studies were conducted in healthy volunteers. During the fluconazole study the potential for fluconazole to adversely affect the pharmacokinetics of azithromycin was also studied. Participants: 24 (cotrimoxazole) and 18 (fluconazole) healthy male and female volunteers. Results: The results of both studies indicated that neither the peak concentrations of nor the exposures (area under the concentration-time curve) to the test drugs were changed when azithromycin was coadministered. In addition, fluconazole did not significantly alter the pharmacokinetic parameters of azithromycin. Conclusions: Azithromycin does not alter the bioavailability of either cotrimoxazole or fluconazole.