D. Kaiser, E. M. Glenn
1972
Citations
0
Influential Citations
47
Citations
Quality indicators
Journal
Journal of pharmaceutical sciences
Abstract
Investigations with 4,5-bis(p-methoxyphenyl)-2-phenylpyrrole-3-acetonitrile, a potent anti-inflammatory, antiarthritic, and antipyretic drug, were undertaken to: (a) develop a simple, rapid, sensitive, and specific method of analysis for the intact drug in biological matrixes; (b) determine the relationship between plasma drug concentrations, administered dose, and anti-inflammatory activity in polyarthritic rats; (c) compare the normalized plasma or serum drug concentrations in rats, dogs, and man when an equivalent oral dose was administered; and (d) estimate the plasma or serum drug disappearance half-life in rats, dogs, and man after single-dose oral drug administration. The results indicated that plasma drug concentrations in the polyarthritic rat, as measured by fluorometric techniques, were dose related. Biological activity, expressed as mean percentage inhibition of arthritis, was related to the logarithm of the average plasma drug concentration (micrograms per milliliter) in a dosage interval at the equilibrium state. After single-dose oral drug administration, at calculated equivalent dose levels (milligrams per kilogram), drug concentrations found in the plasma or serum of human subjects were greater than those found in rats or dogs. The plasma drug disappearance half-life found in man (t½ = 1.5-2.0 hr.) was more similar to dogs (t½ = 1.5-2.0 hr.) than to rats (t½ = 11.4 hr.).