Effect of Gastric Acidity on Bioavailability of N, N-Dimethylcarbamoylmethyl α, 2-Dimethyl-5H-[1]benzopyrano[2, 3-b]pyridine-7-acetate, a New Prodrug-Type Anti-inflammatory Agent

Abstract

The effect of gastric acidity on the bioavailability of N, N-dimethylcarbomoylmethyl α, 2-dimethyl-5H-[1]benzopyrano[2, 3-b]pyridine-7-acetate (1), a new anti-inflammatory agent, was investigated in gastric acidity-controlled beagle dogs.The dissolution rates of this compound in media of pH 1.2 and 3.0 were greater than those in media of pH 5.0 and 6.8. Reflecting these dissolution characteristics, the peak plasma concentration (C_max) and the area under the plasma concentration-time curve (AUC_0-12h) were rduced by shifting the gastric acidity to low levels (more than pH 6) with omeprazole treatmen.In designing dosage forms of 1, it is necessary to develop pharmaceutical preparations whose bioavailability is not affeted by the gastric acidity.