Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast--MK-0679) in asthmatic patients.
The safety, tolerability and bronchodilator properties of inhaled verlukast (MK-0679), a new potent and selective LTD4-receptor antagonist, were studied in 12 asthmatic subjects with more than 15% increase in FEV1 after salbutamol inhalation. On three separate study days the patients inhaled placebo, verlukast 2 mg and verlukast 8 mg from a metered dose inhaler according to a randomized, double-blind, cross-over allocation schedule. Pulmonary function and tolerability were assessed regularly and after 8 h a second dose of test drug was inhaled. Thirty minutes later a beta 2-agonist dose-response curve was performed by inhaling salbutamol in cumulative doses of 200, 400 and 800 micrograms. Verlukast (8 mg) caused significant improvement in mean FEV1 from 1.5 through 8 h after inhalation as compared to placebo (P less than 0.05). The maximum change in FEV1 occurred at 2 h after inhalation with mean percent increases above baseline of 3.5, 7.7, and 9.2% after placebo, verlukast 2 mg and 8 mg, respectively. The bronchodilator response to inhaled salbutamol was significantly larger after verlukast 8 mg than after placebo pretreatment (P less than 0.05), whereas verlukast 2 mg afforded no additive bronchodilator effect. We conclude that inhalation of the LTD4-antagonist verlukast induces modest but significant bronchodilatation and may be beneficial in the treatment of asthma.
Lammers
J W
JW
Department of Pulmonary Diseases, University Hospital, HB Nijmegen, The Netherlands.
Van Daele
P
P
Van den Elshout
F M
FM
Decramer
M
M
Buntinx
A
A
De Lepeleire
I
I
Friedman
B
B
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000008:administration & dosage / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D013189:SRS-A / Q000037:antagonists & inhibitors*
D001993:Bronchodilator Agents; D011422:Propionates; D011804:Quinolines; D013189:SRS-A; C059141:verlukast; D000420:Albuterol