Effect of gastric acidity on bioavailability of N,N-dimethylcarbamoylmethylalpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate, a new prodrug-type anti-inflammatory agent.
The effect of gastric acidity on the bioavailability of N,N-dimethylcarbamoylmethyl alpha,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 (Cmax) and the area under the plasma concentration-time curve (AUC0-12h) were reduced by shifting the gastric acidity to low levels (more than pH 6) with omeprazole treatment. In designing dosage forms of 1, it is necessary to develop pharmaceutical preparations whose bioavailability is not affected by the gastric acidity.
Yamada
I
I
Goda
T
T
Kawata
M
M
Mizuta
H
H
Ogawa
K
K
Yokobe
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001578:Benzopyrans / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D011355:Prodrugs; D011725:Pyridines / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D011355:Prodrugs; D011725:Pyridines; C063558:N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-1-benzopyrano(2,3-b)pyridine-7-acetate