选择性血小板活化因子拮抗剂CV-3988静脉注射给人体后的有效性和耐受性。
Effectiveness and tolerability of CV-3988, a selective PAF antagonist, after intravenous administration to man.
作者信息
Arnout J, van Hecken A, De Lepeleire I, Miyamoto Y, Holmes I, De Schepper P, Vermylen J
机构信息
Department of Pathophysiology, University of Leuven, Belgium.
出版信息
Br J Clin Pharmacol. 1988 Apr;25(4):445-51. doi: 10.1111/j.1365-2125.1988.tb03328.x.
Abstract
- The efficacy and tolerability of CV-3988, a selective PAF antagonist with structural analogies with PAF, were studied after intravenous infusion in man. 2. The compound, in doses from 750 to 2,000 micrograms kg-1, significantly reduced platelet sensitivity for PAF. The threshold aggregating concentration (TAC) of PAF, expressed in % of the mean predosing value, increased in a dose dependent manner reaching 356 +/- 162% of the basal TAC at the end and 266 +/- 123% of the basal TAC 4 h after infusion of the highest dose. The TAC of PAF returned to the basal value within 24 h after the end of the infusion. 3. CV-3988 did not cause major side effects nor changes in blood pressure, pulse and respiratory rate. However, small but clinically insignificant changes in plasma haemoglobin and serum haptoglobin were seen at the end and 4 h after the end of the infusion, indicating a slight haemolysis. 4. Our results indicate that, when adequate infusion volumes and infusion rates are used, CV-3988 can safely be administered to man and should be useful in elucidating the role of PAF in disease.
摘要
- 研究了与人血小板活化因子（PAF）结构类似的选择性PAF拮抗剂CV-3988静脉输注后的疗效和耐受性。2. 该化合物剂量为750至2000微克/千克时，可显著降低血小板对PAF的敏感性。PAF的阈值聚集浓度（TAC），以给药前平均值得百分比表示，呈剂量依赖性增加，在输注最高剂量结束时达到基础TAC的356±162%，输注后4小时达到基础TAC的266±123%。PAF的TAC在输注结束后24小时内恢复到基础值。3. CV-3988未引起重大副作用，也未导致血压、脉搏和呼吸频率变化。然而，在输注结束时和结束后4小时，血浆血红蛋白和血清触珠蛋白出现了微小但临床上无显著意义的变化，表明有轻微溶血。4. 我们的结果表明，当使用适当的输注量和输注速率时，CV-3988可安全地用于人体，且应有助于阐明PAF在疾病中的作用。
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