Development of idraparinux and idrabiotaparinux for anticoagulant therapy.
Idraparinux is an analogue of fondaparinux binding with high affinity to antithrombin. It was designed for weekly, rather than daily, administration, with an exceptionally long half-life. One potential problem with small heparin-like fragments of this type is the difficulty of neutralising excessive activity in the case of side-effects or overdose. The efficacy of idraparinux was was proven in clinical studies with patients suffering from venous thromboembolism (VTE) or atrial fibrillation. Due to major bleeding events during treatment for more than six months the development of idraparinux was stopped. Idrabiotaparinux has an attached biotin moiety at the non-reducing end unit, which allows its neutralisation with avidin, an egg-derived protein with low antigenicity. This compound is currently investigated in clinical trials for prevention of recurrent VTE in patients with acute pulmonary embolism. The future of idrabiotaparinux depends also on the safety and efficacy of avidin.
Harenberg
Job
J
Ruprecht-Karls University Heidelberg, Maybachstrasse 14, D-68169 Mannheim, Germany. job.harenberg@medma.uni-heidelberg.de
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000990:Antithrombin III / Q000037:antagonists & inhibitors / Q000378:metabolism; D001281:Atrial Fibrillation / Q000150:complications; D001360:Avidin / Q000494:pharmacology; D001710:Biotin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006494:Heparin Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011134:Polysaccharides / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
D000925:Anticoagulants; D006494:Heparin Antagonists; D009844:Oligosaccharides; D011134:Polysaccharides; D001360:Avidin; C479958:idraparinux; D001710:Biotin; D000990:Antithrombin III; C545956:idrabiotaparinux; D000077425:Fondaparinux