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| | #REDIRECT [[Eptifibatide#Pharmacology]] |
| {{Eptifibatide}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| ===Mechanism of Action===
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| Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of [[fibrinogen]], [[von Willebrand factor]], and other adhesive ligands to GP IIb/IIIa. When administered intravenously, eptifibatide inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. Platelet aggregation inhibition is reversible following cessation of the eptifibatide infusion; this is thought to result from dissociation of eptifibatide from the platelet.
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| ===Pharmacodynamics===
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| Infusion of eptifibatide into baboons caused a dose-dependent inhibition of ex vivo platelet aggregation, with complete inhibition of aggregation achieved at infusion rates greater than 5 mcg/kg/min. In a baboon model that is refractory to [[aspirin]] and [[heparin]], doses of eptifibatide that inhibit aggregation prevented acute thrombosis with only a modest prolongation (2- to 3-fold) of the bleeding time. Platelet aggregation in dogs was also inhibited by infusions of eptifibatide, with complete inhibition at 2 mcg/kg/min. This infusion dose completely inhibited canine coronary thrombosis induced by coronary artery injury (Folts model).
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| Human pharmacodynamic data were obtained in healthy subjects and in patients presenting with UA or NSTEMI and/or undergoing percutaneous coronary intervention. Studies in healthy subjects enrolled only males; patient studies enrolled approximately one-third women. In these studies, INTEGRILIN inhibited ex vivo platelet aggregation induced by adenosine diphosphate (ADP) and other agonists in a dose- and concentration-dependent manner. The effect of INTEGRILIN was observed immediately after administration of a 180-mcg/kg intravenous bolus. Table 4 shows the effects of dosing regimens of INTEGRILIN used in the IMPACT II and PURSUIT studies on ex vivo platelet aggregation induced by 20 µM ADP in PPACK-anticoagulated platelet-rich plasma and on bleeding time. The effects of the dosing regimen used in ESPRIT on platelet aggregation have not been studied.
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| The INTEGRILIN dosing regimen used in the ESPRIT study included two 180-mcg/kg bolus doses given 10 minutes apart combined with a continuous 2-mcg/kg/min infusion.
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| When administered alone, INTEGRILIN has no measurable effect on PT or aPTT.
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| There were no important differences between men and women or between age groups in the pharmacodynamic properties of eptifibatide. Differences among ethnic groups have not been assessed.
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| ===Pharmacokinetics===
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| The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses ranging from 90 to 250 mcg/kg and infusion rates from 0.5 to 3 mcg/kg/min. Plasma elimination half-life is approximately 2.5 hours. Administration of a single 180-mcg/kg bolus combined with an infusion produces an early peak level, followed by a small decline prior to attaining steady state (within 4-6 hours). This decline can be prevented by administering a second 180-mcg/kg bolus 10 minutes after the first. The extent of eptifibatide binding to human plasma protein is about 25%. Clearance in patients with coronary artery disease is about 55 mL/kg/h. In healthy subjects, renal clearance accounts for approximately 50% of total body clearance, with the majority of the drug excreted in the urine as eptifibatide, deaminated eptifibatide, and other, more polar metabolites. No major metabolites have been detected in human plasma.
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| ===Special Populations===
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| ====Geriatric====
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| Patients in clinical studies were older (range: 20-94 years) than those in the clinical pharmacology studies. Elderly patients with coronary artery disease demonstrated higher plasma levels and lower total body clearance of eptifibatide when given the same dose as younger patients. Limited data are available on lighter weight (<50 kg) patients over 75 years of age.
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| ====Renal Impairment====
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| In patients with moderate to severe [[renal insufficiency]] (CrCl <50 mL/min using the Cockcroft-Gault equation), the clearance of eptifibatide is reduced by approximately 50% and steady-state plasma levels approximately doubled [see Use in Specific Populations (8.6) and Dosage and Administration (2)].
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| ====Hepatic Impairment====
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| No studies have been conducted in patients with hepatic impairment.
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| ====Gender====
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| Males and females have not demonstrated any clinically significant differences in the pharmacokinetics of eptifibatide.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = INTEGRILIN (EPTIFIBATIDE) INJECTION, SOLUTION [MERCK SHARP & DOHME CORP.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5ad82e30-50d8-450c-8a2a-b4b507ed1ce2 | publisher = | date = | accessdate = 5 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Antiplatelet drugs]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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