title: Pharmacodynamic and clinical trials of glycoprotein IIb/IIIa inhibitors and potential relationship of results to dosing.
abstract: Glycoprotein IIb/IIIa inhibitors have become the standard of care for patients undergoing percutaneous coronary intervention (PCI) and for those presenting with non-ST-segment elevation myocardial infarction (NSTE-ACS). Clinical effects of GP IIb/IIIa inhibitors in PCI and NSTE-ACS strongly correlate with potency, consistency, and durability of platelet aggregation inhibition. Under standardized conditions [light transmission aggregometry (LTA), 20 micromol adenosine diphosphate (ADP) as an agonist, and D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK) as an anticoagulant], we demand consistent platelet aggregation inhibition >80% during the time of PCI (initial balloon inflation), and during the entire duration of therapy in NSTE-ACS. The benefit of abciximab (bolus 0.25 mg/kg plus infusion 10 microg/kg/min) correlates with >80% inhibition of platelet aggregation during the intervention (PCI) and immediately thereafter (<6 hours). The absence of a benefit with abciximab in NSTE-ACS is most likely due to <80% inhibition during the major part of the infusion period (>6 hours). Tirofiban does not achieve >80% inhibition at the time of PCI at a dose of 10 microg/kg bolus plus 0.15 microg/kg/min infusion, and at a dose of 0.4 lg/kg/min loading infusion for 30 minutes plus 0.1 microg/kg/min maintenance infusion, the target value is only reached after 18 h. Eptifibatide (double-bolus 180 microg/kg 10 min apart, followed immediately by a 2.0 microg/kg/min infusion) provided an instant, consistent, and durable antiplatelet effect for the entire duration of infusion, and a significant clinical benefit in both PCI (non-ACS patients) and medically managed NSTE-ACS patients.
authors.affiliation: Medizinische Klinik II-Kardiologie, Angiologie, Internistische Intensivmedizin, St. Marien-Krankenhaus Siegen, Kampenstrasse 51, 57072 Siegen, Germany. H-P.HOBBACH@t-online.de
authors.forename: H-P
authors.initials: HP
authors.lastname: Hobbach
authors.forename: P
authors.initials: P
authors.lastname: Schuster
mesh_terms: D000077284:Abciximab; D000789:Angina, Unstable / Q000188:drug therapy; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077542:Eptifibatide; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007263:Infusions, Parenteral; D009203:Myocardial Infarction / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D013997:Time Factors; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab