A physiologically based pharmacokinetic model linking plasma protein binding interactions with drug disposition

Research in Veterinary Science
Jennifer L BuurJim E Riviere

Abstract

Combination drug therapy increases the chance for an adverse drug reactions due to drug-drug interactions. Altered disposition for sulfamethazine (SMZ) when concurrently administered with flunixin meglumine (FLU) in swine could lead to increased tissue residues. There is a need for a pharmacokinetic modeling technique that can predict the consequences of possible drug interactions. A physiologically based pharmacokinetic model was developed that links plasma protein binding interactions to drug disposition for SMZ and FLU in swine. The model predicted a sustained decrease in total drug and a temporary increase in free drug concentration. An in vivo study confirmed the presence of a drug interaction. Neither the model nor the in vivo study revealed clinically significant changes that alter tissue disposition. This novel linkage approach has use in the prediction of the clinical impact of plasma protein binding interactions. Ultimately it could be used in the design of dosing regimens and in the protection of the food supply through prediction and minimization of tissue residues.

References

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Sep 9, 2006·Journal of Veterinary Pharmacology and Therapeutics·J L BuurJ E Riviere

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Citations

Jun 16, 2011·Journal of Veterinary Pharmacology and Therapeutics·T L LeavensJ E Riviere
Aug 4, 2011·Equine Veterinary Journal. Supplement·A J MortonD E Freeman
Oct 19, 2010·Journal of Veterinary Pharmacology and Therapeutics·L G YuanY H Liu
Nov 8, 2014·Journal of Veterinary Pharmacology and Therapeutics·X YangY-H Liu
Nov 17, 2009·Basic & Clinical Pharmacology & Toxicology·Frédéric Y Bois
Aug 2, 2014·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Teresa L LeavensJim E Riviere
Jun 16, 2016·Scientific Reports·Zhoumeng LinJim E Riviere
Jun 20, 2017·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Miao LiZhoumeng Lin
May 2, 2019·The Veterinary Record·Alexandra SchoosDominiek Gd Maes

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