Effect of acetazolamide on the pharmacokinetics of cyclosporin in rabbits

The effect of concomitant intravenous administration of acetazolamide on cyclosporin's pharmacokinetic parameters has been studied in rabbits. The study design was parallel: the control group of six rabbits received cyclosporin alone, while cyclosporin and acetazolamide were co-administered to six rabbits in the second group. Serial blood samples were collected for 24 h following administration of drugs. Cyclosporin concentrations were determined using a specific monoclonal radioimmunoassay. Pharmacokinetic parameters of cyclosporin were derived using compartmental and non-compartmental techniques. Concomitant administration of acetazolamide with cyclosporin resulted in a significant increase in the terminal elimination half-life of cyclosporin, a significant decrease in cyclosporin total body clearance, and a significant increase in the steady-state volume of distribution relative to the control group. The mean residence time of cyclosporin in the peripheral tissue was dramatically increased with the administration of acetazolamide. The results of this investigation demonstrate a possible interaction between acetazolamide and cyclosporin. The most plausible explanation for this is an alteration in the disposition kinetics of cyclosporin. Adjusting the dose of cyclosporin may be required in patients with uveitis receiving both cyclosporin and acetazolamide.