Bivalirudin | Encyclopeptide

Chemical Identity

Property	Value
Chemical Formula	C98H138N24O33
Molecular Weight	2180.3 Da
CAS Number	128270-60-0
Peptide Class	Synthetic 20-amino acid Peptide
Sequence	D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH

Structure

Bivalirudin (Angiomax) is a synthetic 20-amino acid polypeptide analog of hirudin, the anticoagulant from medicinal leeches. It contains a D-phenylalanine at the N-terminus, a thrombin-active site-binding sequence (D-Phe-Pro-Arg-Pro), four glycine residues as a linker, and a C-terminal hirudin-derived sequence that binds exosite I.

Mechanism of Action

Bivalirudin binds thrombin bivalently: the N-terminal D-Phe-Pro-Arg-Pro tetrapeptide reversibly occupies the catalytic site, while the C-terminal dodecapeptide binds exosite I (fibrinogen recognition site). Thrombin slowly cleaves the Arg3-Pro4 bond, regenerating active site function and providing self-limiting anticoagulation.

Clinical Applications

Percutaneous coronary intervention: Anticoagulant during PCI (Angiomax)
Heparin-induced thrombocytopenia: Alternative to heparin during PCI
Acute coronary syndromes: With planned early invasive strategy
STEMI: Primary PCI anticoagulation

Pharmacokinetics

Half-life: 25 minutes
Onset: Immediate (IV bolus)
Protein binding: Negligible
Metabolism: Thrombin cleavage (80%), renal (20%)
Elimination: Renal
Dose adjustment: Required in severe renal impairment

Safety and Side Effects

Bleeding (major 2-3%), back pain, nausea, headache, and injection site pain. Lower risk of HIT compared to heparin. Rapid reversibility due to enzymatic degradation.

References

Lincoff, A.M., et al. (2003). REPLACE-2 trial: bivalirudin during PCI. New England Journal of Medicine, 348, 563-569.
Stone, G.W., et al. (2006). HORIZON-AMI trial: bivalirudin for STEMI. New England Journal of Medicine, 355, 2203-2216.