臨床薬理
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
Aspirinの週1~2回間歇投与法
星 恵子周 新平寺園 美奈子佐藤 安浩山崎 淳子三宅 良彦
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2001 年 32 巻 5 号 p. 223-230

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The efficacy of platelet inhibition with aspirin for the prevention of secondary and primary events in patients with cardiovascular and cerebrovascular diseases is established. Aspirin irreversibly acetylates platelet cyclooxygenese (COX) and permanently inhibits thromboxane A2 production. Platelets do not re-synthesize COX because platelets do not have nucleus. Therefore, active enzyme returns with a time course reflecting platelet turnover (life span 7-10 days). According to the above pharmacological mechanisms of aspirin, an intermittent administration (1-2 times a week) of aspirin is sufficient to obtain the antiplatelet effect.
Eight healthy subjects (3 males: 30-42 years, 5 females: 21-42 years) ingested 81 mg of buffered aspirin. Platelet aggregation was measured before aspirin ingestion and at 90 minutes, 3 days, 5 days, and 7 days after aspirin ingestion of a single 81 mg aspirin . The mean inhibition rate of platelet aggregation was 79.7±7.1% at 90 minutes (p=0.00002), 69.4±15.6% at 3 days (p=0.0002), 44.4±30.0% at 5 days (p=0.003), and 22.1 ±34.8% at 7 days (p=0.048). The inhibition of platelet aggregation of aspirin persisted for five to seven days.
The ratio of small, medium and large-sized aggregates was determined simultaneously. The ratio of small, medium and large was 38: 26: 36 (%) before ingestion respectively, 82: 8.6: 9.4 at 90 minutes, 71: 14: 16 at 3 days, 56: 18: 26 at 5 days, and 47: 21: 32 at 7 days after ingestion of a single 81 mg aspirin. Aspirin mainly inhibited the formation of large-sized platelet aggregates.
The inhibitory effect of platelet aggregation appeared within 5 minutes and the mean inhibition rate (n=5) was 27.1±28.1% at 5 minutes (p=0.06), 57.1±20.4% at 10 minutes (p=0.004), 72.1±13.5% at 15 minutes (p=0.0007), 78.9 ±9% at 20 minutes (p=0.0002), 85.3±9.5% at 25 minutes (p=0.00006), and 84.1±3.9% at 30 minutes (p= 0.00004) after a single 81 mg aspirin ingestion. The data indicated that aspirin is a quick-working medicine. The ratio of large-sized aggregates decreased from 42% to 19.8% in 10 minutes and to only 5.4% in 30 minutes after ingestion.
The present study showed that the inhibitory effect of platelet aggregation of aspirin persisted for at least 5 days or more and that aspirin is a considerably quick working medicine. Thus, it is thought that an intermittent administration of aspirin should be recommended for the secondary and primary prevention of arteriosclerotic diseases.

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