PY 108-068 — Acute effects of a single oral dose in chronic stable angina

PY 108-068 is a dihydropyridine calcium antagonist. In a double-blind, randomised crossover study in 6 patients with chronic stable angina, we compared the acute effects of a single oral dose of placebo with 25 mg and 50 mg of PY 108-068. Investigations were performed on 3 mornings at weekly intervals. Resting supine and erect heart rate and blood pressure were measured before the dose and repeated 75 min later. At approximately 90 min after the dose each patient performed a standardised exercise test on a bicycle ergometer. The mean area (number of points) of ST-segment depression on 16-point precordial exercise maps was 13.1 with placebo, 4.5 with 25 mg of PY 108-068 and 4.3 with 50 mg of PY 108-068 (NS). The rate-pressure product at initial ST-segment depression >1 mm was 15.6×103 with placebo, 17.8×103 with 25 mg of PY 108-068 and 18.5×103 with 50 mg of PY 108-068. Resting supine heart rate was significantly faster with both 25 mg of PY 108-068 (65 beats/min) and 50 mg PY 108-068 (67 beats/min) compared with placebo (59 beats/min). The mean reduction in supine blood pressure from that with placebo was 12/7 mm Hg with 25 mg of PY 108-068 and 10/8 mm Hg with 50 mg of PY 108-068 (NS). These results confirm the modest acute antianginal efficacy of a single oral dose of PY 108-068. The absence of reflex tachycardia found in previous chronic oral dosing studies with this drug appears to take some days to develop in humans.