The Direct Thrombin Inhibitor Argatroban: A Review of Its Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Relationships

ABSTRACT

The direct thrombin inhibitor argatroban exhibits pharmacological properties that are distinctly different from those of other thrombin inhibitors. Within its clinically relevant dose range, argatroban shows linear pharmacokinetic behavior and concentrations that are well correlated with anticoagulant effects. The pharmacokinetic profile can be described by a two-compartment model with first-order elimination. Whereas argatroban does not require dosage modification in patients with renal dysfunction and has been demonstrated to be safe and well tolerated in hemodialysis, dosing precautions are recommended in hepatically impaired patients. The effects of high-dose or prevention therapy can be monitored by various coagulation parameters like activated clotting time (ACT), activated partial thromboplastin time (aPTT), or ecarin clotting time (ECT). Whereas the aPTT response to argatroban varies with aPTT reagent, ECT seems to be a more specific monitoring parameter for the direct thrombin inhibitor. Argatroban influences the prothrombin time, expressed as the international normalized ratio (INR), which complicates the transition to oral anticoagulation with coumarin derivatives. An overlap period with warfarin for a minimum of 4 to 5 days, aimed at an INR of > 4 on a Quick-type prothrombin time assay, is recommended before discontinuation of argatroban therapy. The good predictability of the anticoagulant effect of argatroban, together with its fast clearance and lack of influence by renal dysfunction, makes argatroban an ideal antithrombotic agent in the intensive care unit setting and in interventional cardiology.

Argatroban - pharmacokinetics - pharmacodynamics - monitoring

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