Relationships between biophasic disposition and pharmacokinetic behavior in nonsteroid antiinflammatory drugs

The time course of biophasic amounts of two nonsteroid antiinflammatory drugs (naproxen and oxyphenbutazone) after an intravenous dose of both drugs in rats (5 and 20 mg/kg, respectively) and their relationships with the drug amounts in central and peripheral compartments as defined through blood level data obtained after the same intravenous dose of the drug, are described. To assess the first point, the carrageenin-induced rat paw edema method is employed. Through previously established dose-response curves obtained after administration of different i.v. doses, the conversion of responses to biophasic amounts is achieved by means of the corresponding model equations. To calculate kinetic parameters through the fitting of the concentration-time data, a least-squares method based on the Marquardt algorithm is used on a computer. It can be concluded that the biophasic compartment cannot be identified as the "central" or the "peripheral" kinetic ones, being, however, the output biophasic rate constant not significantly different from the terminal disposition rate constant, beta or lambda 2.