title: The efficacy and safety of clopidogrel resinate as a novel polymeric salt form of clopidogrel.
abstract: 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) 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 2000 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 (Papp) of 13.5 +/- 1.13 x 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.
authors: DDS Research Lab, CKD Research Institute, CKD Pharmaceutical Corp., Chonan 330-831, Korea.
authors: Min-Hyo
authors: MH
authors: Ki
authors: Mee-Hwa
authors: MH
authors: Choi
authors: Kwang-Bok
authors: KB
authors: Ahn
authors: Byoung-Su
authors: BS
authors: Kim
authors: Dai Sig
authors: DS
authors: Im
authors: Soon-Kil
authors: SK
authors: Ahn
authors: Hee-Jong
authors: HJ
authors: Shin
mesh_terms: D000818:Animals; D001760:Bleeding Time; D018938:Caco-2 Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D000077144:Clopidogrel; D004285:Dogs; D004355:Drug Stability; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
chemical_list: D010975:Platelet Aggregation Inhibitors; D011108:Polymers; C528439:clopidogrel resinate; D000077144:Clopidogrel; D013988:Ticlopidine