Bronchodilatation and attenuation of exercise-induced bronchospasm by PY 108-068, a new calcium antagonist

The effect of a new dihydropyridine-derivative calcium antagonist, PY 108-068, on resting and postexercise flow rates was evaluated in 12 adult asthmatic subjects in a double-blind, randomized, placebo-controlled, cross-over study. The study consisted of 2 periods, each lasting for 3 days. For a given period a single dose of PY 108-068 (or placebo) was given orally, 75 mg on the first day and 150 mg on the second and third day. Spirometry was obtained at 30-min intervals thereafter. On Day 3, 75 min after the medication was given, a 6-min treadmill exercise test was performed breathing dry air. The mean maximal FEV1 recorded after 150 mg of PY 108-068 on Day 2 was 15 +/- 4% higher than the daily baseline (p less than 0.05), whereas after placebo the maximal FEV1 value was not different from the daily baseline. Also, the mean FEV1 values, expressed as percent of the daily predrug baseline, were significantly higher at 2 and 3 h after 150 mg of PY 108-068 than the respective values after placebo (110 +/- 4 compared with 95 +/- 1, and 106 +/- 5 compared with 91 +/- 3, respectively). Exercise-induced bronchospasm (EIB), expressed as maximal percent fall in FEV1 from preexercise baseline, was attenuated by PY 108-068 as compared with placebo (% delta FEV1 of 20 +/- 6 and 40 +/- 4, respectively; p less than 0.001). Protection against EIB did not correlate with the resting bronchodilation induced by PY 108-068, but was more likely if the patient had eosinophilia. Thus, PY 108-068 not only attenuates EIB but also causes resting bronchodilation, a unique finding for calcium channel blockers.