Study of drug interaction between the new antiallergic drug 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid and theophylline.
A new chemical compound, 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), known to inhibit the second stage type I allergy and endowed with antiasthmatic action, was investigated with regard to its effects on theophylline (TP) blood level in comparison with ketotifen and tranilast, antiasthmatics of the same therapeutic category as Sm 857, and tiaramide, an antiinflammatory agent. Sm 857 was administered orally to rats at 50 mg/kg, followed by oral administration of TP at 10 mg/kg or intravenous administration of aminophylline 13 mg/kg 10 min later. The concomitant use of Sm 857 apparently lowered the development of TP blood level during 1-5 h after administration when compared with the control. A similar lowering effect on TP blood level was observed at both single and 3-day prior administration of Sm 857. Ketotifen also reduced TP blood level at a dose of 50 mg/kg, while tranilast proved to have almost no such influence on TP blood level. Unlike the mentioned antiasthmatics, tiaramide tended to delay TP clearance. The determination of TP free fraction produced by addition of testing drugs to TP-containing rat serum in vitro after incubation for a certain period of time revealed a 30% increase in free fraction percent in case of Sm 857 addition, 7% increase in case of tranilast addition and no change at all in case of ketotifen and tiaramide addition. Above results suggest that the concomitant use of Sm 857 and TP might cause drug interaction. Sm 857 is thought to increase the blood free fraction of concomitantly used TP and to accelerate elimination of TP from blood.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*
D011799:Quinazolines; D000628:Aminophylline; D013806:Theophylline; C051309:doqualast