CORRELATION OF SERUM INDOXOLE [2,3-BIS(p-METHOXYPHENYL)-INDOLE] LEVELS WITH BIOLOGIC ACTIVITY

¹ The Upjohn Company, Kalamazoo, Michigan

Investigations with indoxole [2,3-bis(p-methoxyphenyl)-indole], a potent antiinflammatory, antiarthritic and antipyretic drug in rats, were undertaken to 1) determine whether a correlation existed between drug serum concentrations, administered dose and antiinfiammatory activity, 2) compare the drug serum levels obtained in various animal species when a constant oral dose was administered in an effective dosage form and 3) select an effective dosage form for oral administration to man. The results indicated that serum indoxole concentrations in the polyarthritic rat, as measured by fluorometric methods, were dose-related. Biologic activity, expressed as mean percentage inhibition of arthritis, was related to the log of the average serum level in a dosage interval at the equilibrium state, expressed in micrograms per milliliter. After oral administration of drug at 50 mg/kg in modified corn oil emulsion, rats, dogs and gerbils attained higher average drug concentrations in serum than did mice, rabbits, guinea pigs, chickens or monkeys. Cottonseed oil, modified corn oil emulsion and polysorbate 80 were the preferred vehicles for drug administration in the dog and rat. As the administration of indoxole in cottonseed oil and modified corn oil emulsion necessitated the ingestion of large volumes of vehicle, polysorbate 80 was selected as the preferred vehicle for oral administration to man.