PMID: 1195454Dec 1, 1975Paper

Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man

The Journal of Urology
F BerglundR Pompeius

Abstract

Treatment with the chemotherapeutic combination of 160 mg. trimethoprim plus 800 mg. sulfamethoxazole twice daily increased the serum creatinine level by an average of 2 mg. per 1. in 21 patients. The effect was clearly reversible. The chemical analysis of creatinine was not affected by the addition of trimethoprim, sulfamethoxazole or their metabolites. In 2 subjects given the drug combination for 12 days renal excretion and 24-hour clearances of creatinine decreased but iothalamate 131I clearance was unchanged. Consequently, the rise in serum creatinine does not indicate any decrease in the glomerular filtration rate. The serum creatinine started to rise within 4 hours after oral administration of a single dose. The rise in serum creatinine could be produced with trimethoprim alone but not with sulfamethoxazole alone. When the plasma creatinine was raised to 100 mg. per l. in healthy subjects (by giving creatinine orally), trimethoprim increased the creatinine levels 10 times as much as at normal plasma levels. The effect was interpreted as a competitive inhibition of the mechanism for tubular secretion of creatinine through the base-secreting pathway.

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