[Effects of flutropium bromide, a new antiasthma drug, with repeated administration on bronchomotor response and hepatic drug metabolizing enzymes].
Effects of flutropium bromide, a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, were investigated on the bronchodilatory activity with repeated inhalations in guinea pigs and on the hepatic drug metabolizing enzyme activities with repeated i.v. administration in rats. Single inhalation of flutropium bromide (0.03%) inhibited the ACh-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. Flutropium bromide (0.03%) was inhaled for 5 min a day by placing the animal in an inhalation box, successively during periods of 14 and 28 days. The bronchodilatory effect of flutropium bromide after 14- or 28-day repeated inhalations was almost the same potency as that after single inhalation. Twenty-eight-day repeated inhalations did not change the body weight curve in guinea pigs; and in addition, 14-day repeated i.v. administration did not change the hepatic drug metabolizing enzyme activities in rats. From the above results, it is indicated that flutropium bromide causes neither reduction in response nor cumulative effect after repeated inhalations, and that the agent maintains the bronchodilatory effect without change in the hepatic drug metabolizing enzyme activities.
Mizuno
H
H
Central Research Laboratory, SS Pharmaceutical Co., Ltd., Chiba, Japan
Kawabata
N
N
Ohno
H
H
Misawa
M
M
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000280:Administration, Inhalation; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001286:Atropine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats
D001286:Atropine Derivatives; D006634:Histamine H1 Antagonists; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; C039778:flutropium bromide; D000109:Acetylcholine