Obesity-related physiological changes and their pharmacokinetic consequences

Abstract

The prevalence of obesity has soared in recent decades, and now is considered as a worldwide problem, with significant health and medical implications. Obesity is often linked to several co-morbidities including diabetes, cardiovascular diseases, and cancers, and a number of drugs are available for the treatment of these diseases. Moreover, obesity can affect various physiological factors including plasma proteins, drug metabolizing enzymes, drug transporters, and blood flow, thereby altering drug absorption, distribution, metabolism, and excretion (ADME). Therefore, information regarding obesity-related physiological changes and their pharmacokinetic consequences is crucial for understanding pharmacokinetics and optimizing drug therapy in obese population. Herein, this article reviews the effects of obesity on physiological factors determining drug ADME and their pharmacokinetic consequences. In addition, a brief summary on animal models of obesity is presented.

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Fig. 1

Abbreviations

CL:

Total body clearance

CLH :

Hepatic clearance

CLR :

Renal clearance

Vd :

Volume of distribution

Tmax :

Time to reach a peak plasma concentration

F:

Extent of absolute oral bioavailability

fu :

Free fraction of a drug in plasma

EH :

Hepatic extraction ratio

NASH:

Non-alcoholic steatohepatitis

NAFLH:

Non-alcoholic fatty liver hepatitis

CPR:

NADPH-cytochrome P450 reductase

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2009-0083533 and 2011-0016040).

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Correspondence to Dae-Duk Kim.

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Cho, SJ., Yoon, IS. & Kim, DD. Obesity-related physiological changes and their pharmacokinetic consequences. Journal of Pharmaceutical Investigation 43, 161–169 (2013). https://doi.org/10.1007/s40005-013-0073-4

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Keywords

  • Obesity
  • Pharmacokinetics
  • Animal models