title: Anagrelide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of thrombocythaemia.
abstract: Anagrelide, an orally active quinazolin, induces thrombocytopenia in humans and has therefore been evaluated for use in conditions associated with thrombocythaemia. In patients with essential or myeloproliferative thrombocythaemia, anagrelide (usually 1 to 4 mg/day) produced sustained reductions in platelet counts for 1 to more than 28 months and also reduced the incidence of disease-related symptoms. 60 to 93% of patients responded to anagrelide therapy with clinically significant reductions in platelet count. Anagrelide has a tolerability profile different from that of most other agents used in the treatment of thrombocythaemia; most adverse effects are related to its vasodilatory or positive inotropic properties. Anagrelide has a high specificity towards megakaryocytes (and thus decreases platelet levels), although haematocrit is also reduced in some patients. If longer term trials confirm the lack of leukaemogenic and mutagenic potential with this drug, anagrelide may become the agent of choice for the treatment of thrombocythaemia, especially in younger patients in whom the risk of leukaemogenic transformation with some alternative drugs is of particular concern.
authors.affiliation: Adis International Limited, Auckland, New Zealand.
authors.forename: C M
authors.initials: CM
authors.lastname: Spencer
authors.forename: R N
authors.initials: RN
authors.lastname: Brogden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D013922:Thrombocytosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide