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 < 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 (%ΔFEV₁ of 20 ± 6 and 40 ± 4, respectively; p < 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.