Effect of co-trimoxazole and sulfamethoxazole on serum creatinine in normal subjects.

Significant elevation of serum creatinine concentration and reduction in creatinine clearance have been reported following cotrimoxazole therapy in patients with normal and impaired renal function. Both components of co-trimoxazole, trimethoprim and sulfamethoxazole, have been proposed as the causative agent. Ten healthy male volunteers were treated for seven days with either sulfamethoxazole (5 subjects) or co-trimoxazole (5 subjects) in the usual recommended doses. After a one-week recovery period, the subjects were allocated to the alternate treatment regimen for another seven days. Cotrimoxazole caused a mean elevation in the serum creatinine concentration of 0.12 mg/dl over the base-line value (p less than 0.05). Sulfamethoxazole produced an insignificant fall in the serum creatinine level. The increase in the serum creatinine concentration induced by co-trimoxazole was reversed seven days after discontinuation of the drug. From this study, it can be concluded that either trimethoprim alone or an interaction between trimethoprim and sulfamethoxazole is responsible for the increase in serum creatinine observed following co-trimoxazole therapy and that sulfamethoxazole alone is not the causative agent.