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Effect of cardiometabolic syndrome on drug pharmacokinetics: obesity and hyperlipidemia Open Access


Other title
Cardiometabolic syndrome
Roux-en-Y gastric bypass
Type of item
Degree grantor
University of Alberta
Author or creator
Ben-Eltriki,Mohamed Ahmed
Supervisor and department
Dr. Dion R. Brocks, Faculty of Pharmacy and Pharmaceutical Sciences
Examining committee member and department
Dr. Arno Siraki, Faculty of Pharmacy and Pharmaceutical Sciences
Dr. Dion R. Brocks, Faculty of Pharmacy and Pharmaceutical Sciences
Dr. Glen Baker, Department of Psychiatry, Faculty of Medicine & Dentistry
Dr. Ayman El-Kadi, Faculty of Pharmacy and Pharmaceutical Sciences
Faculty of Pharmacy and Pharmaceutical Sciences
Pharmaceutical Sciences
Date accepted
Graduation date
Master of Science
Degree level
Cardiometabolic syndrome refers to a clustering of several risk factors for cardiovascular disease; obesity and hyperlipidemia are two underlying disorders associated with the syndrome. An often overlooked aspect of these conditions is the effect that they may have on the pharmacokinetics of drugs. In this thesis, the influence of obesity and hyperlipidemia on drug pharmacokinetic was explored using as test drugs azithromycin and cyclosporine. An LC-MS assay for azithromycin was developed and used in a pharmacokinetic study in obese patients. The results were comparable to literature data from lean subjects. Azithromycin bioavailability was reduced by one-third in gastric bypass subjects. Mean leptin and interleukin 6 levels were higher than previously reported for lean subjects. Although in rat hepatocytes lipoproteins had significant down-regulating effects on the mRNA levels of several genes, cyclosporine uptake was minimally affected. In conclusion, our findings could explain some variability in drug pharmacokinetic and unexpected dose versus effect outcomes in cardiometabolic syndrome that could contribute to both hyperlipidemia and obesity state.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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