METABOLISM AND PHARMACOKINETICS OF A NEW NONSTEROID, ANTI-INFLAMMATORY AGENT, 2-(3-CHLORO-o-TOLUIDINO) NICOTINIC ACID (CLONIXIN) IN RATS, DOGS AND MONKEYS

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

Clonixin [2-(3-chloro-o-toluidino)nicotinic acid] is well absorbed by rats, monkeys and dogs. In 24 hours, rats and monkeys excrete more than 60% and dogs about 30% of an i.v. 10 mg/kg dose in the urine. In 72 hours, rats excrete more than 90%, monkeys more than 80% and dogs 74% of the dose in urine and feces. Rats and monkeys excrete drug mainly in urine; dogs, about equally in urine and feces. Clonixin is rapidly metabolized by all three species to its 4'-hydroxy, 5-hydroxy and 2'-hydroxymethyl derivatives. Clonixin plasma levels fit an open two-compartment model in rats and dogs. Plasma elimination rate constants decline with increasing dose, but the excretion pattern is constant. Comparison of areas under the oral and i.v. plasma level curves suggests clonixin is partially metabolized by the gastrointestinal tract or on its first pass through the liver after absorption.