| Indication |
Argatroban is indicated for prevention and treatment of thrombosis
caused by heparin induced thrombocytopenia (HIT). It is also indicated
for use in patients with, or at risk for, HIT who are undergoing
percutaneous coronary intervention. |
| Pharmacodynamics |
Argatroban is a synthetic direct thrombin inhibitor derived from
L-arginine indicated as an anticoagulant for prophylaxis or treatment
of thrombosis in patients with heparin-induced thrombocytopenia.
Argatroban is a direct thrombin inhibitor that reversibly binds to the
thrombin active site. Argatroban does not require the co-factor
antithrombin III for antithrombotic activity. Argatroban exerts its
anticoagulant effects by inhibiting thrombin-catalyzed or -induced
reactions, including fibrin formation; activation of coagulation factors
V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is
highly selective for thrombin with an inhibitory constant (Ki)
of 0.04 µM. At therapeutic concentrations, Argatroban has little or no
effect on related serine proteases (trypsin, factor Xa, plasmin, and
kallikrein).
Argatroban is capable of inhibiting the action of both free and
clot-associated thrombin. |
| Mechanism of action |
Argatroban exerts its anticoagulant effects by inhibiting
thrombin-catalyzed or -induced reactions, including fibrin formation;
activation of coagulation factors V, VIII, and XIII; protein C; and
platelet aggregation. |
| Absorption |
Bioavailability is 100% (intravenous). |
| Volume of distribution |
- 174 mL/kg
- 12.18 L [70-kg adult]
|
| Protein binding |
54% |
| Metabolism |
Liver via hydroxylation and aromatization of the
3-methyltetrahydroquinoline ring. Age and gender do not substantially
affect the pharmacodynamic or pharmacokinetic profile of argatroban. |
| Route of elimination |
Argatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine. |
| Half life |
39 and 51 minutes |
| Clearance |
- 5.1 L/kg/hr [infusion doses up to 40 mcg/kg/min]
|
| Toxicity |
Excessive bleeding |
