EFFECT OF ACETAZOLAMIDE ON THE PHARMACOKINETICS OF CYCLOSPORINE IN RABBITS

The effect of concomitant intravenous administration of acetazolamide on cyclosporin's pharmacokinetic parameters has been studied in rabbit s. The study design was parallel: the control group of six rabbits rec eived cyclosporin alone, while cyclosporin and acetazolamide were co-a dministered to six rabbits in the second group. Serial blood samples w ere collected for 24 h following administration of drugs. Cyclosporin concentrations were determined using a specific monoclonal radioimmuno assay. Pharmacokinetic parameters of cyclosporin were derived using co mpartmental and non-compartmental techniques. Concomitant administrati on of acetazolamide with cyclosporin resulted in a significant increas e in the terminal elimination half-life of cyclosporin, a significant decrease in cyclosporin total body clearance, and a significant increa se 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 b etween acetazolamide and cyclosporin. The most plausible explanation f or this is an alteration in the disposition kinetics of cyclosporin. A djusting the dose of cyclosporin may be required in patients with uvei tis receiving both cyclosporin and acetazolamide.