Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist
| Autor: | Suellen P. Ferraris, Mary Wethington, Julie H. Oestreich, Jennifer J. Oh, Wendell S. Akers, Steven R. Steinhubl |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Pharmacology chemistry.chemical_compound Bolus (medicine) P2Y12 Cangrelor Pharmacokinetics Purinergic P2 Receptor Antagonists Humans Medicine Pharmacology (medical) Dosing Infusions Intravenous Injections Intraventricular business.industry Platelet Activation Clopidogrel Adenosine Monophosphate Receptors Purinergic P2Y12 P-Selectin Tolerability chemistry Pharmacodynamics Anesthesia Female business Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 50:27-35 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270009344986 |
| Popis: | 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-microg/kg bolus followed by a 2-microg/kg/min infusion or a 30-microg/kg bolus followed by a 4-microg/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. |
| Databáze: | OpenAIRE |
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