酵素阻害剤
This anticoagulant (FW = 508.64 g/mol; CAS 74863-84-6), also named
(2R,4R) -4-methyl-1-N2-[ (3-methyl-1,2,3,4-tetrahydro-8-quinolilyl) sulfon-
yl]-L-arginyl-2-piperidine carboxylic acid, Novastan?, and MD-805, is a
direct thrombin inhibitor (1-11) that is an effective treatment for heparin-
induced thrombocytopenia (HIT), an immunoglobulin-mediated adverse
drug reaction characterized by platelet activation, thrombocytopenia, and a
high risk of thrombotic complications among patients who are receiving or
have recently received heparin. HIT is an autoimmune-like disorder, with
the target antigen a multimolecular complex of the “self” protein, Platelet
Factor-4, and heparin. Continued use of heparin is ill-advised and
dangerous. Argatroban is also indicated for the treatment of heparin-
induced thrombocytopenia and thrombosis syndrome (HITTS), an immune-
mediated response to the administration of heparin that results in life-
threatening thrombosis. Argatroban is one of four FDA-approved
parenteral direct thrombin inhibitors, the others being lepirudin, desirudin,
and bivalirudin. Argatroban is metabolized in the liver (t1/2 = ~50 min).
Other DTI’s include recombinant hirudins, bivalirudin, and ximelagatran,
either alone or in combination with melagatran. Argatroban is a
significantly weaker inhibitor of trypsin, K = 4.3 μM, plasmin (K =
ii
800 μM), coagulation factor Xa, and plasma kallikrein (Ki = 2 mM).
Commercial sources often supply a mixture of 21 (R) and 21 (S)
Diastereoisomers. The latter is more potent.
