PY108-068, a New Calcium Antagonist, with Nifedipine in Exercise-Induced Asthma Outcomes

Article shows research outcomes based on data which is given in this article.

Twelve of 16 subjects completed the study. Four subjects dropped out after the first day (two due to exacerbations of asthma thought unrelated to the study, one due to lack of cooperation, and one due to an unrelated illness).

Resting bronchodilation, expressed as mean percentage of change in FEW from baseline, is shown in Figure 1. The peak bronchodilator effect of nifedipine occurred at one-half and one hour, while that for 150 mg of PY 108-068 occurred two hours after administration of the drug. Only nifedipine caused a significant increase in FEV1 as compared to placebo by the Schefife test.

The increase in heart rate above baseline at two hours was significantly more after taking 150 mg of PY 108-068 (16 ± 4 beats per minute; mean ± SD), as compared to 75 mg (2 ±2 beats per minute), nifedipine (5 ±2 beats per minute), and placebo (— 3 ± 2 beats per minute). Systolic blood pressure did not vary significantly among the four drugs. Diastolic blood pressure decreased significantly two hours after 75 mg of PY 108-068 (-8 ±3 mm Hg) and after 150 mg (-9±3 mm Hg), compared to placebo (4 ±2 mm Hg). Diastolic blood pressure after 150 mg of PY 108-068 was also significantly lower than after nifedipine ( —6±3 mm Hg) at two hours after the drug.

Use Inhaler at Exercise-Induced Asthma

All subjects completed the exercise protocol. The stimulus for bronchospasm was the same in that there were no differences in the maximum minute ventilation, heart rate, and maximum oxygen uptake achieved on each occasion. Bronchospasm and dyspnea were evident after nearly every bout of exercise, with maximal reduction in flow rates 6 to 15 minutes after cessation of exercise. Only the mean percentage of change in FEV1 after 150 mg of PY 108-068 (24 ± 13) was significantly less than placebo (40 ± 16). The maximum falls in FEV1 after exercise for 75 mg of PY 108-068 and nifedipine were 26 ± 15 and 29 ± 11, respectively; individual changes in FEVi associated with each drug are shown in Table 1.

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Headache was a frequent side effect, occurring in six subjects after nifedipine, five after 150 mg of PY 108-068, one after 75 mg of PY 108-068, and none after placebo. It was subjectively more severe after nifedipine. One subject complained of palpitations and another complained of lightheadedness 30 minutes after taking nifedipine. No significant laboratory abnormalities were detected at the end of the study.

Table 1—Maximal Percentage of Change in FEV, after Exercise

PY108-068
Subject Placebo 75 mg 150 mg Nifedipine
1 30 15 43 35
2 37 27 44 20
3 64 53 31 20
4 52 13 10 35
5 60 38 30 48
6 54 39 24 39
7 51 48 5 37
8 30 11 21 16
9 16 15 10 38
10 22 23 29 23
11 40 21 29 15
12 25 15 11 24
Mean ± SD 40± 16 26± 15 24± 13 29± 11

 

change-in-FEV1

Figure 1. Percentage of change in FEV1 before exercise (mean SE; N = 12) from baseline at 30, 60, 90, and 120 minutes after nifedipine (squares), placebo (triangles), 150 mg of PY 108-068 (<diamonds), and 75 mg of PY 108-068 (circles).