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| __NOTOC__
| | #REDIRECT [[Tirofiban#Pharmacology]] |
| {{Tirofiban}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| === Mechanism of Action===
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| AGGRASTAT is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, AGGRASTAT inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner.
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| When given according to the PRISM-PLUS regimen of 0.4 mcg/kg/min for 30 minutes followed by a 0.1 mcg/kg/min maintenance infusion, >90% inhibition of platelet aggregation is attained by the end of the 30-minute infusion. When given according to the recommended regimen of 25 mcg/kg over 3 min followed by a 0.15 mcg/kg/min maintenance infusion, >90% inhibition of platelet aggregation is attained within 10 minutes. Platelet aggregation inhibition is reversible following cessation of the infusion of AGGRASTAT.
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| ===Pharmacodynamics===
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| AGGRASTAT inhibits platelet function, as demonstrated by its ability to inhibit ex vivo adenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time in healthy subjects and patients with coronary artery disease. The time course of inhibition parallels the plasma concentration profile of the drug.
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| Following discontinuation of an infusion of AGGRASTAT 0.10 mcg/kg/min, ex vivo platelet aggregation returns to near baseline in 4 to 8 hours in approximately 90% of patients with coronary artery disease. The addition of [[heparin]] to this regimen does not significantly alter the percentage of subjects with >70% inhibition of platelet aggregation ([[IPA]]), but does increase the average bleeding time, as well as the number of patients with bleeding times prolonged to >30 minutes. Similar platelet aggregation recovery rates are observed following discontinuation of a 0.15 mcg/kg/min infusion.
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| ===Pharmacokinetics===
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| Tirofiban has a half-life of approximately 2 hours. It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban. Metabolism appears to be limited. | |
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| Tirofiban is not highly bound to plasma proteins and protein binding is concentration independent over the range of 0.01 to 25 mcg/mL. The unbound fraction in human plasma is 35%. The steady state volume of distribution of tirofiban ranges from 22 to 42 liters.
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| In healthy subjects, the plasma clearance of tirofiban ranges from 213 to 314 mL/min. Renal clearance accounts for 39 to 69% of plasma clearance.
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| ====Special Populations====
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| There is no effect on clearance of tirofiban by sex, race, age, or hepatic impairment.
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| =====Renal Insufficiency=====
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| Plasma clearance of tirofiban is decreased about 40% in subjects with creatinine clearance <60 mL/min and >50% in patients with creatinine clearance <30 mL/min, including patients requiring hemodialysis [see Dosage and Administration (2)]. Tirofiban is removed by hemodialysis.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = AGGRASTAT (TIROFIBAN) INJECTION, SOLUTION [MEDICURE INTERNATIONAL INC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fe0ced75-ccbf-4d2e-bd0d-b57e60ab913f | publisher = | date = | accessdate = 6 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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