Renal handling and effects of S(+)‐ibuprofen and R(–)‐ibuprofen in the rat isolated perfused kidney

1 The renal handling and effects of S(+)‐ and R(–)‐ibuprofen have been studied in the isolated perfused kidney (IPK) of the rat. 2 Both ibuprofen enantiomers were extensively reabsorbed and accumulated in the kidney in a concentration‐dependent manner. No pharmacokinetic differences were observed between the two enantiomers. 3 S(+)‐ibuprofen concentrations ranging from 0.25 to 25 μg ml−1 (1.2 to 120 μm) caused a decrease in urinary flow, glomerular filtration rate (GFR) and electrolyte excretion. Urinary pH and excretion of glucose were not influenced. R(–)‐ibuprofen concentrations ranging from 2.5 to 25 μg ml−1 (12 to 120 μm) also decreased urinary flow and electrolyte excretion. This decrease, however, was less than observed with S(+)‐ibuprofen. GFR, urinary pH and glucose excretion were not affected by R(–)‐ibuprofen. Prostaglandin E2 (PGE2) concentrations of 133 ng ml−1 reversed the effects on renal function of both enantiomers. 4 Very high S(+)‐ and R(–)‐ibuprofen concentrations (> 400 μg ml−1) resulted in an increase in urinary flow and fractional excretion of sodium, chloride, potassium, glucose and calcium. 5 It is concluded that the pharmacokinetic behaviour of ibuprofen in the kidney is not stereoselective. Relatively high concentrations of both enantiomers increased the urinary flow and electrolyte excretion in a nonstereoselective manner. Lower concentrations of S(+)‐ibuprofen decreased urinary flow and electrolyte excretion. The pharmacologically inactive R(–)‐ibuprofen was also able to affect renal function in a similar way, but at different concentrations. These effects on renal function are probably caused by inhibition of PGE2 synthesis.