Pharmacodynamics of abciximab during angioplasty: comparison to healthy subjects

Clinical Pharmacology and Therapeutics
Darrell R AbernethyJane Freedman

Abstract

Our objectives were to compare and contrast abciximab concentration-effect relationships in healthy volunteer participants with those in patients with coronary atherosclerosis undergoing elective coronary angioplasty. We also aimed to establish abciximab plasma concentrations associated with 80% inhibition of platelet aggregation. Abciximab clearance and concentration-effect relationships were determined from two separate clinical studies, one in 30 healthy subjects aged 21 to 66 years and the other in 32 patients aged 44 to 74 years before they underwent elective coronary angioplasty. After abciximab administration, abciximab plasma concentrations, platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor occupancy, and degree of inhibition of platelet aggregation in the presence of 5-micromol/L and 20-micromol/L adenosine diphosphate was determined. With an E(max) (receptor occupancy) or inhibitory E(max) (inhibition of platelet aggregation) model, abciximab concentrations required for 80% receptor occupancy and 80% inhibition of platelet aggregation were determined. Abciximab steady-state clearance in healthy participants was 183 +/- 72 ml/min (mean +/- SD), and single-dose clearance in patients undergoing angioplasty was 405 +/...Continue Reading

Citations

Apr 6, 2006·BMC Cardiovascular Disorders·Rainer VoisardVinzenz Hombach
Sep 7, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yeamin HuhMeihau Rose Feng
Oct 4, 2005·Journal of Pharmaceutical Sciences·Donald E MagerDarrell R Abernethy
Oct 17, 2006·Wiener medizinische Wochenschrift·Florian B Mayr, Bernd Jilma
Dec 13, 2006·Journal of Thrombosis and Thrombolysis·Enrico RomagnoliFilippo Crea
Jun 25, 2009·Journal of Thrombosis and Haemostasis : JTH·H E SpeichL K Jennings
Oct 10, 2003·The Journal of Pharmacology and Experimental Therapeutics·Donald E MagerDarrell R Abernethy

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