Trimethoprim-sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant recipients.

Aims The influence of the trimethoprim-sulphamethoxazole combination on the steady-state pharmacokinetics of sirolimus, a potent macrocyclic immunosuppressant, was studied in renal transplant recipients. Methods Fifteen kidney transplant recipients were treated with sirolimus 8-23 mg m(-2) in combination with azathioprine and prednisolone from the day of transplantation. Whole blood sirolimus AUC and C-max were determined on days 6 and 7 after transplantation. On day 7, sirolimus was coadministered with the first dose of trimethoprim (80 mg) and sulphamethoxazole (400 mg). Results On day 6, the mean (95% confidence interval) whole blood sirolimus AUC((0-24 h)) was 1040 (846, 1234) ng ml(-1) and mean C-max was 109 (88, 129) ng ml(-1). Corresponding values on day 7 were AUC((0-24 h)) 1060 (826, 1293) ng ml(-1) and C-max mean 107 (87, 127) ng ml(-1). The mean difference in the dose-corrected AUC((0-24 h)) was 0.40% (-9.4, +10). Conclusions A single dose of trimethoprim-sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant patients.