Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study

Objectives This pilot study sought to assess the metabolism of Plavix (Bristol-Myers Squibb/Sanofi) and generic clopidogrel in cats, using a novel assay for the measurement of clopidogrel, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM-D). Methods This was a prospective, ra...

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Veröffentlicht in:Journal of feline medicine and surgery 2019-10, Vol.21 (10), p.951-958
Hauptverfasser: Malkawi, Mays, Woolcock, Andrew D, Lee, Pamela M, Court, Michael H, Moore, George E, Hogan, Daniel F
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container_end_page 958
container_issue 10
container_start_page 951
container_title Journal of feline medicine and surgery
container_volume 21
creator Malkawi, Mays
Woolcock, Andrew D
Lee, Pamela M
Court, Michael H
Moore, George E
Hogan, Daniel F
description Objectives This pilot study sought to assess the metabolism of Plavix (Bristol-Myers Squibb/Sanofi) and generic clopidogrel in cats, using a novel assay for the measurement of clopidogrel, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM-D). Methods This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). Results The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80–1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. Conclusions and relevance This is the first study comparing Plavix and generic clopidogrel in cats. Administration of the generic formulation resulted in comparable plasma concentrations of clopidogrel active metabolite when compared with Plavix.
doi_str_mv 10.1177/1098612X18810887
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Methods This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). Results The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80–1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. Conclusions and relevance This is the first study comparing Plavix and generic clopidogrel in cats. Administration of the generic formulation resulted in comparable plasma concentrations of clopidogrel active metabolite when compared with Plavix.</description><identifier>ISSN: 1098-612X</identifier><identifier>EISSN: 1532-2750</identifier><identifier>DOI: 10.1177/1098612X18810887</identifier><identifier>PMID: 30427274</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Blood Platelets - drug effects ; Cat Diseases - drug therapy ; Cats - metabolism ; Clopidogrel - administration &amp; dosage ; Double-Blind Method ; Female ; Male ; Metabolomics ; Original ; Pilot Projects ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - administration &amp; dosage ; Prospective Studies</subject><ispartof>Journal of feline medicine and surgery, 2019-10, Vol.21 (10), p.951-958</ispartof><rights>The Author(s) 2018</rights><rights>The Author(s) 2018 2018 International Society of Feline Medicine and American Association of Feline Practitioners</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-93977a0a910c1eba8450ad4de8fce6c2db5a36a200f8ad43a9be762492d02b703</citedby><cites>FETCH-LOGICAL-c435t-93977a0a910c1eba8450ad4de8fce6c2db5a36a200f8ad43a9be762492d02b703</cites><orcidid>0000-0001-6003-0496 ; 0000-0001-7102-3224 ; 0000-0001-9091-572X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132235/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132235/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,21965,27852,27923,27924,44944,45332,53790,53792</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/1098612X18810887?utm_source=summon&amp;utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30427274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Malkawi, Mays</creatorcontrib><creatorcontrib>Woolcock, Andrew D</creatorcontrib><creatorcontrib>Lee, Pamela M</creatorcontrib><creatorcontrib>Court, Michael H</creatorcontrib><creatorcontrib>Moore, George E</creatorcontrib><creatorcontrib>Hogan, Daniel F</creatorcontrib><title>Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study</title><title>Journal of feline medicine and surgery</title><addtitle>J Feline Med Surg</addtitle><description>Objectives This pilot study sought to assess the metabolism of Plavix (Bristol-Myers Squibb/Sanofi) and generic clopidogrel in cats, using a novel assay for the measurement of clopidogrel, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM-D). Methods This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). Results The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80–1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. Conclusions and relevance This is the first study comparing Plavix and generic clopidogrel in cats. 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Methods This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). Results The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80–1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. Conclusions and relevance This is the first study comparing Plavix and generic clopidogrel in cats. 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subjects Animals
Blood Platelets - drug effects
Cat Diseases - drug therapy
Cats - metabolism
Clopidogrel - administration & dosage
Double-Blind Method
Female
Male
Metabolomics
Original
Pilot Projects
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - administration & dosage
Prospective Studies
title Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study
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