Bivalirudin

Molecular formula Cg8Hi38N24C 33 Molecular weight 2180.28 CAS Registry No 128270-60-0 Merck Index 13,1306 

Sample preparation Condition a 1 mL 30 mg Oasis HLB SPE cartridge with 1 ml. MeCNitrifluoroacetic acid 98 2 and 1 mT. water. Plasma. Mix 200 lL plasma with 100 xL of a solution of IS in water, make up to 1100 iL with water, add 1 mL to the SPE cartridge, wash with 500 aL water, wash with 500 (jiL MeOHrwater 30 70, elute with 1 mL MeCN trifluoroacetic acid 98 2, evaporate the eluate to dr5mess under a stream of nitrogen at 40°, reconstitute the residue with 100 aL MeOH water 50 50, centrifuge at 10 000 rpm at 4° for 10 min, inject a 30 iL aUquot. Urine. Mix 50 aL urine with 400 xL of a solution of IS in water, make up to 500 iaL with water, inject a 10 aL aliquot. 

Mobile phase Gradient. A B from 30 70 to 100 0 over 0.5 min, maintain at 100 0 for 2 min, return to initial conditions over 0.2 min, re-equihhrate at initial conditions for 1.5 min. A was MeCN 0.1% formic acid 60 40. B was 0.1% formic acid. 

Internal standard Gln-9-hirulog (Polypeptide Laboratories, Torrance CA) (m/z 1097.9 to 199.1) 

Robson, R. White, H. Aylward, P. Frampton, C. Bivalirudin pharmacokinetics and phsirmacodynamics effect of renal function, dose, and gender, Clin.Pharmacol.Ther., 2002, 71, 433-439. 

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Bivalirudin Used as an alternative to heparin during cardiopulmonary bypass in patients with a history if HIT... 

Given that thrombin is the central mediator of coagulation and amplifies its own production, it is a natural target for pharmacologic intervention. Direct thrombin inhibitors (DTIs) bind thrombin and prevent interactions with its substrates (Fig. 7-7). Several injectable DTIs are approved for use in the United States including lepirudin, bivalirudin, arga-troban, and desirudin. Several oral DTIs are currently in... 

For patients with NSTE ACS undergoing planned early angiography and revascularization with PCI, UFH, LMWH (enoxaparin), fondaparinux, or bivalirudin should be administered. Therapy should be continued for up to 48 hours for UFH, until the patient is discharged, or a maximum of 8 days for either enoxaparin or fondaparinux, and until the end of the PCI or angiography procedure (or up to 42 hours after PCI) for bivalirudin. 

Bivalirudin (55 Angiomax ) Hirudin Peptide Synthetic congener Animal Antittirombotic Specific and reversible direct thrombin inhibitor (DTI) 479 91... 

Bivalirudin directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine proteinase that plays a central... 

Gladwell TD. (2002) Bivalirudin A direct thrombin inhibitor. Clin Ther 24 38-58. 

Warkentin TE, Greinacher A, Koster A. (2008) Bivalirudin. Thromb Haemost 99 830-839. 

Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Eeit F, Colombo A, Aylward PE, Cequier AR, Darius H, Desmet W, Ebrahimi R, Hamon M, Rasmussen LH, Rupprecht H-J, Hoekstra J, Mehran R, Ohman EM. (2006) Bivalirudin for patients with acute coronary syndromes. N EnglJ Med 355 2203-2216. 

Bittl JA, Chaitman BR, Feit F, Kimball W, Topol EJ. (2001) Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina Final report reanalysis of the bivalirudin angioplasty study. Am Heart J142 952-959. 

Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G Carr J, Cohen EA, Betriu A, Desmet W, Kereiakes DJ, Rutsch W, Wilcox RG de Feyter PJ, Vahanian A, Topol EJ. (2003) Bivalirudin and provisional glycoprotein Ilb/IIIa blockade compared with heparin and planned glycoprotein Ilb/nia blockade during percutaneous coronary intervention REPLACE-2 randomized trial. J Am Med Assoc (JAMA) 289 853-863. 

Wong SC, Kirtane AJ, Parise H, Mehran R. (2008) Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 358 2218-2230. 

For further information http //en.wikipedia.org/wiki/Bivalirudin (accessed on 14.12.2010). 

Concomitant aspirin therapy Bivalirudin is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin. 

The safety and efficacy of bivalirudin have not been established in patients with acute coronary syndromes who are not undergoing percutaneous transluminal coronary angioplasty (PTCA) or percutaneous coronary intervention (PCI). 

PCI Bivalirudin with provisional use of glycoprotein llb/llla inhibitor (GPIIb/llla inhibitor) is indicated for use as an anticoagulant in patients undergoing PCI. 

The recommended dosage of bivalirudin is an intravenous (IV) bolus dose of 0.75 mg/kg. This should be followed by an infusion of 1.75 mg/kg/h for the duration of the PCI procedure. Five minutes after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed. GPIIb/llla inhibitor administration should be considered in the event that any of the following conditions are present ... 

HIT/HITTS The recommended dose of bivalirudin in patients with HIT/HITTS undergoing PCI is an IV bolus dose of 0.75 mg/kg. This should be followed by a... 

Administer bivalirudin via an IV line. Do not mix other medications with bivalirudin before or during administration. No incompatibilities have been observed with glass bottles or polyvinyl chloride bags and administration sets. 

Bivalirudin does not bind to plasma proteins (other than thrombin) or to red blood cells. 

Bivalirudin Pharmacokinetic Parameters and Dose Adjustments in Renal Impairment ... 

Active major bleeding hypersensitivity to bivalirudin or any of its components. 

Hematologic effects Bivalirudin is not intended for intramuscular administration. Although most bleeding associated with the use of bivalirudin in PCI occurs at the site of arterial puncture, hemorrhage can occur at any site. 

Brachytherapy An increased risk of thrombus formation has been associated with the use of bivalirudin in gamma brachytherapy, including fatal outcomes. 

Elderly In studies of patients undergoing PCI, 44% were 65 years of age and older, and 12% were older than 75 years of age. Elderly patients experienced more bleeding events than younger patients. Patients treated with bivalirudin experienced fewer bleeding events in each age stratum, compared with heparin. 

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