Role of Extracellular Ionized Calcium in the In Vitro Assessment of GPIIb/IIIa Receptor Antagonists
dc.contributor.author | Rebello, Sam S. | en_US |
dc.contributor.author | Huang, Jinbao | en_US |
dc.contributor.author | Faul, Jessica D. | en_US |
dc.contributor.author | Lucchesi, Benedict Robert | en_US |
dc.date.accessioned | 2006-09-11T19:41:51Z | |
dc.date.available | 2006-09-11T19:41:51Z | |
dc.date.issued | 2000-01 | en_US |
dc.identifier.citation | Rebello, Sam S.; Huang, Jinbao; Faul, Jessica D.; Lucchesi, Benedict R.; (2000). "Role of Extracellular Ionized Calcium in the In Vitro Assessment of GPIIb/IIIa Receptor Antagonists." Journal of Thrombosis and Thrombolysis 9(1): 23-28. <http://hdl.handle.net/2027.42/48046> | en_US |
dc.identifier.issn | 0929-5305 | en_US |
dc.identifier.issn | 1573-742X | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/48046 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10590185&dopt=citation | en_US |
dc.description.abstract | Several preclinical studies have found a poor correlation between the ex vivo platelet inhibitory potency and the in vivo antithrombotic efficacy of GPIIb/IIIa receptor antagonists. The present study was designed to examine the differential in vitro potencies of c7E3, MK-383, DMP-728, and SM-20302 in inhibiting ex vivo platelet aggregation under normocalcemic and hypocalcemic conditions. Human blood was collected in either trisodium citrate (0.37%) or PPACK (20 µg/mL). Platelet aggregation assays were performed in platelet-rich plasma from citrate-anticoagulated blood (cPRP) and PPACK-anticoagulated blood (pPRP) using ADP (20 µM) and TRAP (10 µM) as agonists in the presence of c7E3, MK-383, DMP-728, or SM-20302. The concentration of ionized calcium in cPRP was 16–19 times lower than that in pPRP. The IC 50 of c7E3 for inhibiting ADP-induced platelet aggregation in cPRP (2.76 ± 0.11 µg/mL) was 1.6 times lower than that in pPRP (4.46 ± 0.48 µg/mL; P < 0.05). Similarly, the IC 50 for c7E3 for inhibiting TRAP-induced platelet aggregation in cPRP (4.52 ± 0.34 µg/mL) was 1.7 times lower than that in pPRP (7.69 ± 0.43 µg/mL; P < 0.05). MK-383, DMP-728, and SM-20302 also demonstrated 1.96-, 1.15-, and 1.43-fold lower IC 50 values, respectively, in cPRP as compared with pPRP. Chelation of ionized calcium in pPRP led to a progressive increase in platelet inhibition by all the antagonists. These results suggest that the observed in vitro inhibitory potency of a GPIIb/IIIa receptor antagonist is markedly enhanced when trisodium citrate is used as an anticoagulant to collect blood for ex vivo assay. These findings indicate that dosing regimens for GPIIb/IIIa receptor antagonists based on the platelet inhibition profile in citrate may provide misleading information with respect to their true in vivo antithrombotic efficacy. | en_US |
dc.format.extent | 125637 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers; Springer Science+Business Media | en_US |
dc.subject.other | Medicine & Public Health | en_US |
dc.subject.other | Cardiology | en_US |
dc.subject.other | Hematology | en_US |
dc.subject.other | GPIIb/IIIa | en_US |
dc.subject.other | Trisodium Citrate | en_US |
dc.subject.other | PPACK (Phe-Pro-Arg Chloromethyl Ketone) | en_US |
dc.subject.other | Platelet Aggregation | en_US |
dc.title | Role of Extracellular Ionized Calcium in the In Vitro Assessment of GPIIb/IIIa Receptor Antagonists | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 10590185 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/48046/1/11239_2004_Article_202949.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1023/A:1018679708251 | en_US |
dc.identifier.source | Journal of Thrombosis and Thrombolysis | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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