Population pharmacodynamic modelling of aspirin- and Ibuprofen-induced inhibition of platelet aggregation in healthy subjects

Clinical Pharmacokinetics
Ying HongDonald E Mager

Abstract

The objective of this study was to develop a mechanism-based pharmacodynamic model that characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. Ten healthy volunteers were enrolled in a single-blinded, randomized, three-way crossover study. Treatments consisted of single doses of oral aspirin (325 mg) and ibuprofen (400 mg) and concomitant administration of aspirin (325 mg) and ibuprofen (400 mg). Ex vivo whole blood platelet aggregation induced by collagen (1 microg/mL) or arachidonic acid (0.5 mmol/L) was measured by impedance aggregometry. Model development and population parameter estimation were performed using nonlinear mixed-effects modelling implemented in NONMEM. Relatively complete inhibition of platelet aggregation was achieved following aspirin treatment (approximately 77% inhibition within 2 hours), and return to baseline values occurred within 72-96 hours after dosing. In contrast, treatment with ibuprofen alone or in combination with aspirin produced transient inhibition of platelet aggregation, with complete recovery observed in 6-8 hours. The final pharmacodynamic model was based on the turnover of cyclo-oxygenase-1 (COX-1) enzyme, and incorporated irreve...Continue Reading

References

Nov 1, 1990·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·P C ElwoodS Renaud
Dec 1, 1985·Circulation·C PatronoL Forni
Dec 1, 1995·Journal of Clinical Pharmacology·I H BenedekD M Kornhauser
Mar 27, 1998·Clinical Pharmacokinetics·N M Davies
Jun 25, 1998·Irish Journal of Medical Science·L O'NeillP O'Regan
Apr 24, 1999·The Biochemical Journal·J K GierseP C Isakson
Jun 9, 2000·Cardiology·M E McKenzieV L Serebruany
Nov 23, 2000·The New England Journal of Medicine·C BombardierUNKNOWN VIGOR Study Group
Oct 31, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·A AbelöM O Karlsson
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·M OuelletM D Percival
Dec 26, 2001·The New England Journal of Medicine·F Catella-LawsonG A FitzGerald
Apr 20, 2005·Journal of the American College of Cardiology·Marta L CaponePaola Patrignani
Oct 4, 2005·Expert Opinion on Pharmacotherapy·Udaya S TantryPaul A Gurbel
Aug 8, 2006·Clinical Pharmacology and Therapeutics·Maria G SciulliPaola Patrignani
Sep 6, 2006·Clinical Pharmacology and Therapeutics·Giulia RendaPaola Patrignani

❮ Previous
Next ❯

Citations

Dec 2, 2009·Inflammopharmacology·K D Rainsford
Apr 12, 2013·Journal of Fluorescence·Lin WangMatthew E McCarroll
Jun 2, 2011·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Howard S Smith
Jun 7, 2014·Expert Opinion on Drug Safety·Srinivas NalamachuRobert Taylor
Oct 21, 2015·Expert Opinion on Drug Discovery·Wilhelmus E A de WitteElizabeth C M de Lange
Oct 13, 2015·British Journal of Clinical Pharmacology·Mark RuzovDavid Stepensky
Mar 13, 2014·Basic & Clinical Pharmacology & Toxicology·Hwi-yeol YunKwang-il Kwon
May 19, 2018·Journal of Clinical Pharmacology·Erica S WestphalFran M Gengo
Feb 23, 2019·The Journal of Pharmacy and Pharmacology·Ioannis Loisios-KonstantinidisJennifer Dressman
Mar 27, 2019·Clinical Pharmacology and Therapeutics·Jin NiuDonald E Mager
May 20, 2018·Journal of Pharmacokinetics and Pharmacodynamics·Wilhelmus E A de WitteElizabeth C M de Lange
Nov 27, 2019·Cellular and Molecular Life Sciences : CMLS·Fabrizio ClarelliPia Abel Zur Wiesch
Oct 7, 2017·Sports Medicine - Open·Martin Anthony Christopher ManoukianCharles DeMesa
Jul 29, 2008·Current Opinion in Anaesthesiology

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.