Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist

被引:140
作者
Akers, Wendell S. [1 ]
Oh, Jennifer J. [2 ]
Oestreich, Julie H. [2 ]
Ferraris, Suellen [3 ]
Wethington, Mary [4 ]
Steinhubl, Steven R. [5 ]
机构
[1] Lipscomb Univ, Dept Pharmaceut Sci, Coll Pharm, Nashville, TN 37204 USA
[2] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY USA
[3] Univ Kentucky, Dept Surg, Lexington, KY USA
[4] Clin Res Org, Lexington, KY USA
[5] Medicines Co, Zurich, Switzerland
关键词
Cangrelor; P2Y(12); pharmacodynamics; pharmacokinetics; clopidogrel; PERCUTANEOUS CORONARY INTERVENTION; MYOCARDIAL-INFARCTION; CLOPIDOGREL; ASPIRIN; THERAPY; TOLERABILITY; AR-C69931MX; SAFETY;
D O I
10.1177/0091270009344986
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty-two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15-mu g/kg bolus followed by a 2-mu g/kg/min infusion or a 30-mu g/kg bolus followed by a 4-mu g/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters. Administration of an intravenous bolus followed by a continuous infusion rapidly achieves maximum concentrations of cangrelor that are associated with extensive platelet inhibition within 2 minutes. Moreover, extensive platelet inhibition is maintained throughout the infusion period with near-full recovery of platelet function within 60 to 90 minutes of terminating the infusion. The effect of high-dose cangrelor is more consistent and demonstrates a greater level of inhibition on adenosine diphosphate-induced P-selectin expression; how-ever, no significant differences are observed between the 2 dosing regimens with regard to platelet aggregation or time to recovery of platelet function. Cangrelor administered as an intravenous bolus followed by a continuous infusion in healthy volunteers offers rapid and reversible inhibition of platelet function.
引用
收藏
页码:27 / 35
页数:9
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