DISPOSITION OF CLONIXIN [2-(3-CHLORO-o-TOLUIDINO) NICOTINIC ACID] IN HUMANS

¹ Department of Biochemistry, Biological Research Division, Schering Corporation, Bloomfield, New Jersey

These studies were designed to gain insight into the pharmacodynamics and pharmacokinetics of clonixin in humans and to determine the degree of similarity of human and animal excretion and urine metabolite patterns. Clonixin is rapidly absorbed and excreted by humans. Peak plasma levels are attained in one hour; in 24 hours, 62% of an oral 500-mg dose is excreted in the urine and less than 1% in the feces. In 120 hours 86% is excreted in urine and feces. Clonixin is the major compound found in plasma up to six hours after drug administration, but clonixin and 4'-OH clonixin—and to a lesser extent, 5-OH clonixin and the 2'-CH₂OH metabolite—are the major compounds excreted in 0- to 24-hour urine. Clonixin plasma levels fit an open one-compartment model (k_a = 1.35, k_e = 0.48 and = V_d 0.1l2 1/kg), and are not measurable 16 hours after drug administration. Human and rhesus monkey urine excretion patterns are quantitatively similar and the urine metabolite patterns are qualitatively similar. The similarity of these patterns suggests that clonixin activity and toxicity shisould be similar in both species.