Open AccessUR‐3216: A Manageable Oral GPIIb/IIIa Antagonist
Author(s) -
Baba Kosuke,
Aga Yasuhiro,
Nakanishi Takayuki,
Motoyama Takahiro,
Ueno Hitoshi
Publication year - 2001
Publication title -
cardiovascular drug reviews
Language(s) - English
Resource type - Journals
eISSN - 1527-3466
pISSN - 0897-5957
DOI - 10.1111/j.1527-3466.2001.tb00181.x
Subject(s) - abciximab , platelet , pharmacology , medicine , antagonist , prodrug , platelet aggregation inhibitor , chemistry , receptor , myocardial infarction , conventional pci
UR‐3216, a prodrug, is a novel, selective, and orally active platelet surface glycoprotein GPIIb/IIIa) receptor antagonist. The most important property of UR‐3216 is the very tight binding of its active metabolite to platelets ( K i for resting platelets is <1 nM). UR‐2992, the active form of UR‐3216, binds to platelets for a long period of time, while the unbound drug is rapidly cleared. Therefore, after an initial loading dose of 0.1 mg/kg, only once daily repeated low maintenance doses of UR‐3216 (<0.05 mg/kg p.o.) are required. This regimen maintains a high level of inhibition of platelet aggregation and, due to a small peak‐to‐trough ratio, severe bleeding is avoided. The therapy with UR‐3216 is easy to manage, because it has low peak‐to‐trough ratio and high efficacy (>80% inhibition of platelet aggregation). In addition, UR‐3216 does not produce excessive bleeding or thrombocytopenia and does not interact with abciximab. UR‐3216 is excreted mostly in bile, so that it will not accumulate in patients with chronic renal dysfunction. UR‐2316 has the following abciximab‐like features: (a) its half‐lives for residence on platelets, inhibition of platelets aggregation and bleeding time prolongation are 60 to 80 h, 24, and 2 h, respectively; (b) its receptor binding occupancy is similar to that of abciximab (Mab1 is inhibited and Mab2 is unaltered). In conclusion, UR‐3216 is a promising, orally active GPIIb/IIIa antagonist for the treatment of cardiovascular diseases.