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Effect of cardiometabolic syndrome on drug pharmacokinetics: obesity and hyperlipidemia

  • Author / Creator
    Ben-Eltriki,Mohamed Ahmed
  • 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.

  • Subjects / Keywords
  • Graduation date
    2012-09
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3PX3H
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Faculty of Pharmacy and Pharmaceutical Sciences
  • Specialization
    • Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
    • Dr. Dion R. Brocks, Faculty of Pharmacy and Pharmaceutical Sciences
  • Examining committee members and their departments
    • Dr. Ayman El-Kadi, Faculty of Pharmacy and Pharmaceutical Sciences
    • Dr. Glen Baker, Department of Psychiatry, Faculty of Medicine & Dentistry
    • Dr. Dion R. Brocks, Faculty of Pharmacy and Pharmaceutical Sciences
    • Dr. Arno Siraki, Faculty of Pharmacy and Pharmaceutical Sciences