Effect of dietary protein on renal tubular clearance of drugs in humans.

Diet is one of many factors that influence the pharmacokinetics of drugs. The level of protein intake has been found to significantly influence drug metabolism and glomerular filtration, both of which play an important role in the clearance of drugs. Recently, a marked change, resulting from restricted dietary protein intake, has been reported in the handling of several drugs which are reabsorbed and/or secreted by the renal tubules. In studies of healthy volunteers on protein-restricted diets the renal clearance and fractional excretion of model compounds have been altered, falling to 30% of values obtained on normal diets in the case of the weak acids oxipurinol and uric acid; the fractional excretion of the weak base cimetidine has been increased by 30%. These studies have also found that the change in the renal clearance of both acids is sustained with prolonged dietary protein-calorie restriction, and that, for oxipurinol, the magnitude of the change is directly related to the quantity of protein in the diet, the change is related specifically to the protein content in the diet (and not the total calories), the onset of change is rapid, and on a low-protein diet the renal clearance undergoes marked diurnal variation. The mechanism for the alteration in tubular function is not clear, but may be related to renal haemodynamic changes or competition for transport associated with protein intake. Regardless of the mechanism, these results have important implications for pharmacokinetic research and clinical practice.