RENAL EXCRETION AND URICOSURIC PROPERTIES OF HALOFENATE, A HYPOLIPIDEMIC-URICOSURIC AGENT, IN THE CHIMPANZEE

Halofenate free acid (HFA) is actively secreted and passively reabsorbed by the renal tubules of the chimpanzee. The active or carrier-mediated secretory component is operative throughout the range of urinary pH and is inhibited by probenecid and p -aminohippurate. In the acid range, the excretion of HFA is not influenced by mannitol osmotic diuresis. In the alkaline range, the excretion and clearance of HFA appear to be markedly increased and to be further augmented by increases in urine flow. Apparent volume dependence at alkaline pH is interpreted cautiously, for a small change in pH (7.35-7.85) can bring about a large difference in nonionic reabsorption. Tubular reabsorption of HFA, when demonstrable, is readily explained in terms of passive back diffusion of the un-ionized fraction because of the pKa (∼3.0) and marked lipid solubility. The uricosuric activity of HFA, under these experimental conditions, is not as great as comparable doses of probenecid although the mechanism of action is presumably the same. Clofibrate free acid was not uricosuric when administered orally to the chimpanzee.