3-HYDROXY-2-PHENYLCINCHONINIC ACID (HPC): ITS ABSORPTIOX, EXCRETION, AND ITS EFFECTS ON CERTAIN RENAL FUNCTIONS AND ENZYME SYSTEMS

¹ The Pharmacology Section, Research Division, Sharp and Dohme, Inc., Glenolden, Pa.

Certain cinchoninic acid derivatives, particularly 3-hydroxy-2-phenylcinchoninic acid (HPC), are unusual with regard to the multiplicity of pharmacodynamic actions that are resident in a single type of structure. The antidiuretic effect that is manifested acutely hut not during chronic administration, the depression of the cardiovascular system when HPC is administered rapidly by venoclysis, the inhibition of intestinal activity and the several other effects to which reference has been made serve as examples of these broad actions of HPC.

HPC appears to be well absorbed from the gastrointestinal tract although itspeak blood level frequently occurs several hours following its oral administration. Its renal clearance is unusually low and the duration of its determinable blood level following a given dose persists for many hours. Although the greater than 90 per cent binding to plasma protein contributes to its renal economy, it is probable that reabsorption of most of the glomerular ultrafiltered increment and a Slow rate of metabolism also account in large measure for its persistence in the body.

The inhibition of phenol red, PAH and penicillin renal tubular secretions by HPC and its enzymologic characteristics as they relate to the inhibition of PAB conjugation without affecting glucose transphosphorylation suggest that this effect of HPC is analogous to those of carinamide and Benemid. However, except for this point of similarity the two types of compounds differ almost qualitatively in the specificity of action of the former group and the multiplicity of the pharmacodynamic actions of HPC. This suggests that additional fundamental studies of the enzymologic properties of this agent should prove fruitful.