The Efficacy and Safety of Clopidogrel Resinate as A Novel Polymeric Salt Form of Clopidogrel

• Published in: Archives of pharmacal research Vol. 31; no. 2; pp. 250 - 258
• Main Authors: Ki, Min-Hyo, Choi, Mee-Hwa, Ahn, Kwang-Bok, Kim, Byoung-Su, Im, Dai-Sig, Ahn, Soon-Kil, Shin, Hee-jong
• Format: Journal Article
• Language: Korean
• Published: 2008
• Subjects: Pharmacodynamics; Stability; Polymeric salt; Safety; Clopidogrel resinate; Pharmacokinetics
• ISSN: 0253-6269; 1976-3786

A novel polymeric salt of clopidogrel, clopidogrel resinate, was prepared as a anticoagulant drug. To prove the feasibility as a new active substance, clopidogrel resinate was evaluated for its efficacy and safety. In accelerated stability tests, the clopidogrel resinate tablet $(Pregrel^{(R)})$ showed less brown discoloration and fewer impurities than the clopidogrel bisulfate tablets under open and closed conditions. In toxicity tests, no deaths occurred after a single dose of up to 2,000 mg/kg/day and 13-week repeated doses of up to 625 mg/kg/day in rats without abnormal symptoms compared to clopidogrel bisulfate. When clopidogrel resinate was treated onto Caco-2 cell monolayers, clopidogrel, but not the resin, permeated across the cells with a hight permeation coefficient $(P_{app})$ of $13.5{\pm}1.13{\times}10^{-6}$ cm/sec. Clopidogrel resinate and clopidogrel bisulfate showed similar pharmacokinetics following oral administration to beagle dogs. A single oral administration of clopidogrel resinate dose-dependently inhibited ADP-induced ex vivo aggregation up to 30 mg/kg in rats. In conclusion, clopidogrel resinate was proved to be an efficient and safe polymeric salt as a candidate for a new clopidogrel salt.