Practical issues in the development of argatroban: a perspective.

Argatroban was the very first antithrombin agent that was approved for clinical use. It represents a synthetic arginomimetic drug with multiple pharmacologic properties. Unlike other antithrombin drugs, argatroban is a reversible antithrombin agent. Furthermore, it modulates endothelial cell function and downregulates various inflammatory and thrombotic cytokines. Argatroban is an effective anticoagulant agent, which at equivalent anticoagulant levels (activated clotting time; ACT) produces a stronger anticoagulant effect in comparison to heparins and hirudins. At a comparable ACT (300 s), argatroban produces much stronger inhibition of thrombin generation as measured by F(1.2) and thrombin-antithrombin complex generation. Argatroban does not generate any neutralizing or non-neutralizing antibodies and, therefore, it does not require any dosage adjustment during the course of therapy as other thrombin inhibitors require. The pharmacological profile of argatroban is unique as this antithrombin drug not only inhibits thrombogenesis but also modulates cellular functions. Because of its broad spectral actions, argatroban will have more expanded indications.