Experimental studies on the nephrotoxicity of pentamidine in rats

Renal side-effects are frequently observed after parenteral administration of pentamidine. In this study in a rat model, the nephrotoxicity was assessed by measuring urinary loss of tubular cells, malate dehydrogenase activity and creatinine clearance. In addition, we studied the influence of other nephrotoxins such as tobramycin, amphotericin B and cyclosporin on the pentamidine-associated nephrotoxicity and proved the possibilities of reducing this toxicity by coadministration with other drugs. The tubular toxicity of pentamidine (1, 10 or 20 mg/kg daily) is dose-related and reversible. The toxicity can be reduced by coadministration of fosfomycin (1 x 500 or 2 x 250 mg/kg daily) and D-glucaro-1,5-lactam (2 x 5 mg/kg daily) and enhanced by tobramycin (2 x 2.5 mg/kg daily), amphotericin B (1 mg/kg daily) and cyclosporin (10 mg/kg daily). Furthermore, an increase in the creatinine clearance in pentamidine-treated rats can be obtained with both verapamil (2 x 1.5 mg/kg daily) and enalapril (5 mg/kg daily).