Detail of "144457-28-3"

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Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol

All Rights Reserved. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. Tang, Man; Mukundan, Madhu; Yang, Jian; Charpentier, Nathan; LeCluyse, Edward L.; Black, Chris; Yang, Dongfang; Shi, Deshi; Yan, Bingfang (Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA). Journal of Pharmacology and Experimental Therapeutics, 319(3), 1467-1476 (English) 2006 American Society for Pharmacology and Experimental Therapeutics. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Aspirin (acetylsalicylic acid) and clopidogrel are two major antithrombogenic agents that are widely used for the treatment and prevention of cerebro- and cardiovascular conditions such as stroke. Combined use produces enhanced therapeutic effect. Aspirin and clopidogrel both are esters, and hydrolysis leads to decreased or inactivated therapeutic activity. The aim of the study was to det. whether aspirin and clopidogrel are hydrolyzed by the same enzyme(s), thus reciprocally prolonging the antithrombogenic activity. To test this possibility, microsomes from the liver and intestine were assayed for the hydrolysis of aspirin and clopidogrel. In contrary to the hypothesis, aspirin and clopidogrel were hydrolyzed in a tissue-differential manner. Liver microsomes hydrolyzed both drugs, whereas intestinal microsomes hydrolyzed aspirin only. Consistent with the tissue distribution of two carboxylesterases human carboxylesterase (HCE) 1 and HCE2, recombinant HCE1 hydrolyzed clopidogrel, whereas recombinant HCE2 hydrolyzed aspirin. In addn., hydrolysis of clopidogrel among liver samples was correlated well with the level of HCE1, and hydrolysis of aspirin with HCE2. Certain natural variants differed from the wild-type enzymes on the hydrolysis of aspirin or clopidogrel. In the presence of Et alc., clopidogrel is converted to Et clopidogrel. Carboxylesterases are important pharmacol. determinants for drugs contg. ester linkages and exhibit a large interindividual variation. 69-72-7 and 144457-28-3 are just another two chemicals used in this study. The isoform-specific hydrolysis of aspirin and clopidogrel suggests that these two antithrombogenic agents may have pharmacokinetic interactions with different sets of ester drugs, and the altered hydrolysis by polymorphic mutants provides a mol. explanation to the interindividual variation. .

Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study

All Rights Reserved. Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study. Souri, Effat; Jalalizadeh, Hassan; Kebriaee-Zadeh, Abbas; Shekarchi, Maral; Dalvandi, Afshin (Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14155-6451, Iran). Biomedical Chromatography, 20(12), 1309-1314 (English) 2006 John Wiley & Sons Ltd. CODEN: BICHE2. ISSN: 0269-3879. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A new, simple, and reproducible method for the detn. of the carboxylic acid metabolite of clopidogrel in human plasma was developed. After liq.-liq. extn. in acidic medium with chloroform, samples were quantified on a Nova-pak C8, 5-mm column using a mixt. of 30 mM K2HPO4-THF-acetonitrile (pH = 3, :19, vol./vol./vol.) as mobile phase with UV detection at 220 nm. The flow rate was set at 0.9 mL/min. Ticlopidine was used as internal std. and the total run time of anal. was ~12 min. The method was linear over the range 0.2-10 mg/mL of clopidogrel metabolite in plasma (r2 > 0.999). The within-day and between-day precision values were in the range 1.0-4.8%. The limit of quantification of the method was 0.2 mg/mL. The method was successfully used to study the pharmacokinetics of clopidogrel in healthy volunteers.Except for chemicals metioned above, 113665-84-2 and 144457-28-3 are also used. .