The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects

Clin Nephrol. 2001 Jan;55(1):45-52.


Background: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion.

Aim: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects.

Methods: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily.

Results: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent.

Conclusions: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Infective Agents / pharmacology*
  • Humans
  • Middle Aged
  • Potassium / metabolism*
  • Prosopagnosia
  • Reference Values
  • Trimethoprim / pharmacology*
  • Uric Acid / metabolism*


  • Anti-Infective Agents
  • Uric Acid
  • Trimethoprim
  • Potassium