Clinical Pharmacokinetics

, Volume 50, Issue 12, pp 825–826 | Cite as

Obesity and Its Impact on Drug Therapy

Are We Ready for This Change?
  • Michael Neely
  • Stan Louie

The prevalence of obesity, defined as a body mass index (BMI) of 30 or more, has dramatically increased over the past 20 years. In 1990, the prevalence of obesity was less than 15% in each of 44 surveyed US states. By 2010, every state in the US had an obesity prevalence of more than 20%.[1] Although this trend appears to be plateauing across all ages, approximately 34% of US adults and 17% of children and adolescents are now obese.[2,3] Obesity has numerous effects on health, which are yet to be fully understood, not the least of which is how we dose therapeutic drugs in these patients. Simple adjustments based on total body weight or some component of it (e.g. lean body weight) cannot be applied across all patients or drugs, since changes in blood volume, organ size or metabolic capacity, and other factors are not uniformly related to body weight alone.[4,5]

Ghobadi et al.[6] have taken an important step forward to quantify the impact of obesity and morbid obesity (BMI ≥40 kg/m2) on...


Obesity PBPK Model Drug Pharmacokinetic Drug Development Process Lean Body Weight 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dr Neely holds an academic licence for Simcyp software. He has received no monetary support from Simcyp. Dr Louie has no conflicts of interest that are directly relevant to the content of this commentary.


  1. 1.
    Centers for Disease Control and Prevention. Overweight and obesity: data and statistics. US obesity trends [online]. Available from URL: [Accessed 2011 Sep 9]
  2. 2.
    Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010; 303(3): 235–41PubMedCrossRefGoogle Scholar
  3. 3.
    Olds T, Maher C, Zumin S, et al. Evidence that the prevalence of childhood overweight is plateauing: data from nine countries. Int J Pediatr Obes 2011; 6(5–6): 342–60PubMedCrossRefGoogle Scholar
  4. 4.
    Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39(3): 215–31PubMedCrossRefGoogle Scholar
  5. 5.
    Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 2010; 49(2): 71–87PubMedCrossRefGoogle Scholar
  6. 6.
    Ghobadi C, Johnson TN, Aarabi M, et al. Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Clin Pharmacokinet 2011; 50(12): 809–22PubMedCrossRefGoogle Scholar
  7. 7.
    Zhao P, Zhang L, Grillo JA, et al. Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther 2011; 89(2): 259–67PubMedCrossRefGoogle Scholar
  8. 8.
    Jiang W, Kim S, Zhang X, et al. The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation. Int J Pharm 2011; 418(2): 151–60PubMedCrossRefGoogle Scholar
  9. 9.
    Mortensen A, Lenz K, AbildstrØm H, et al. Anesthetizing the obese child. Paed Anaesth 2011; 21(6): 623–9CrossRefGoogle Scholar
  10. 10.
    Mulla H, Johnson TN. Dosing dilemmas in obese children. Arch Dis Child Educ Pract Ed 2010; 95(4): 112–7PubMedCrossRefGoogle Scholar
  11. 11.
    Anderson BJ, Holford NHG. Tips and traps analyzing pediatric PK data. Paed Anaesth 2011; 21(3): 222–37CrossRefGoogle Scholar
  12. 12.
    Jain R, Chung SM, Jain L, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther 2011; 90(1): 77–89PubMedCrossRefGoogle Scholar
  13. 13.
    Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259(5091): 87–91PubMedCrossRefGoogle Scholar
  14. 14.
    Hotamisligil GS, Arner P, Caro JF, et al. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95(5): 2409–15PubMedCrossRefGoogle Scholar
  15. 15.
    Hotamisligil GS, Johnson RS, Distel RJ, et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274(5291): 1377–9PubMedCrossRefGoogle Scholar
  16. 16.
    Florez H, Castillo-Florez S, Mendez A, et al. C-reactive protein is elevated in obese patients with the metabolic syndrome. Diabetes Res Clin Pract 2006; 71(1): 92–100PubMedCrossRefGoogle Scholar
  17. 17.
    Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 2005; 33(Pt 5): 1078–81PubMedGoogle Scholar
  18. 18.
    Aitken AE, Morgan ET. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos 2007; 35(9): 1687–93PubMedCrossRefGoogle Scholar
  19. 19.
    Sugioka N, Haraya K, Fukushima K, et al. Effects of obesity induced by high-fat diet on the pharmacokinetics of nelfinavir, a HIV protease inhibitor, in laboratory rats. Biopharm Drug Dispos 2009; 30(9): 532–41PubMedCrossRefGoogle Scholar
  20. 20.
    Cheng Q, Aleksunes LM, Manautou JE, et al. Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity. Mol Pharm 2008; 5(1): 77–91PubMedCrossRefGoogle Scholar
  21. 21.
    Geier A, Dietrich CG, Grote T, et al. Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat. J Hepatol 2005; 43(6): 1021–30PubMedCrossRefGoogle Scholar
  22. 22.
    Le Vee M, Gripon P, Stieger B, et al. Down-regulation of organic anion transporter expression in human hepatocytes exposed to the proinflammatory cytokine interleukin 1beta. Drug Metab Dispos 2008; 36(2): 217–22PubMedCrossRefGoogle Scholar
  23. 23.
    Vee ML, Lecureur V, Stieger B, et al. Regulation of drug transporter expression in human hepatocytes exposed to the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-6. Drug Metab Dispos 2009; 37(3): 685–93PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA

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