The effect of oral diltiazem on airway reactivity to methacholine and exercise in subjects with mild intermittent asthma.
The effect of increasing doses of oral diltiazem on airway reactivity to methacholine was evaluated in 10 volunteers with mild asthma. Then the highest tolerated dose was compared with placebo in preventing exercise-induced bronchoconstriction. Methacholine challenges were performed 1 h before and 100 min after placebo or after 30, 60, 90, 120, or 180 mg of oral diltiazem, given in a single-blind, crossover manner on different days within 2 wk. Diltiazem, at doses above 60 mg prolonged the P-R interval of the electrocardiograph but had no significant effect on FVC, FEV1, or FEF25-75. The mean +/- SEM ratio of the dose of methacholine required to produce a 20% decrease in FEV1 (PD20) after diltiazem to the PD20 before diltiazem, i.e., the fold increase in PD20, was not significantly different from placebo at any dose: 0.93 +/- 0.11 after placebo, 1.2 +/- 0.1 after 30 mg, 1.3 +/- 0.3 after 60 mg, 1.2 +/- 0.2 after 90 mg, 1.1 +/- 0.1 after 120 mg, and 1.0 +/- 0.1 after 180 mg. One hundred minutes before a standardized exercise challenge, 120 to 180 mg of oral diltiazem and identically appearing placebo tablets were administered in a randomized, double-blind, crossover design on separate days at least 48 h apart. The mean +/- SEM maximal postexercise decrease in FEV1 was 25.5 +/- 3.3% after placebo and 17.0 +/- 4.8% after diltiazem (p less than 0.01). There was no correlation between change in FEV1 and serum concentrations of diltiazem or its active metabolite desacetyldiltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)
Harman
E
E
Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville 32610.
Hill
M
M
Fiebelman
R
R
Pieper
J
J
Hendeles
L
L
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors*; D005082:Physical Exertion; D011897:Random Allocation
D008688:Methacholine Compounds; D016210:Methacholine Chloride; D004110:Diltiazem