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.