Skip to main content
SpringerLink
Log in
Book cover

Drug Discovery and Evaluation: Methods in Clinical Pharmacology pp 1–25Cite as

Special Populations: Profiling the Effect of Obesity on Drug Disposition and Pharmacodynamics

  • Living reference work entry
  • First Online:

Abstract

The health implications of obesity remain a global issue with approximately 13% of the world’s population categorized as obese (body mass index [BMI] ≥30 kg/m2) in 2016 (World Health Organization, Obesity and overweight. http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 8 Oct 2018, 2018). Obesity is typically a consequence of either excess food intake, lack of physical activity, genetic predisposition, or a combination thereof. Its impact is multifaceted, not only on the patient’s health leading to a myriad of disease states directly related to obesity, but also on the management of these diseases and other common medical conditions that frequently occur. Obesity-related changes in normal physiology, such as alterations in lipid content, plasma proteins, drug metabolizing enzymes, drug transporters, and blood flow, can affect the disposition (absorption, distribution, metabolism, and excretion) and pharmacodynamics of commonly prescribed drugs, thereby altering their pharmacologic profiles. Hence, an understanding of these pharmacologic changes is necessary to ensure proper treatment is exercised. Unfortunately, our understanding of obesity-related changes in drug pharmacology in addition to the overall safety and efficacy is limited, as clinical trials rarely focus specifically on this population. Therefore, the purpose of this chapter is to provide a review of the available literature assessing the effects of obesity on the disposition and pharmacodynamics of some of the most commonly prescribed drugs. This chapter is a review only; careful clinical decision making should always be used when applying literature from the population to individual patients and scenarios.

This is a preview of subscription content, log in via an institution.

References and Further Reading

  • Abernethy DR, Schwartz JB (1988) Verapamil pharmacodynamics and disposition in obese hypertensive patients. J Cardiovasc Pharmacol 11(2):209–215

    Article  CAS  PubMed  Google Scholar 

  • Abernethy DR, Greenblatt DJ, Smith TW (1981) Digoxin disposition in obesity: clinical pharmacokinetic investigation. Am Heart J 102(4):740–744

    Article  CAS  PubMed  Google Scholar 

  • Abernethy DR, Greenblatt DJ, Divoll M et al (1984) The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet 9(2):177–183

    Article  CAS  PubMed  Google Scholar 

  • Adane ED, Herald M, Koura F (2015) Pharmacokinetics of vancomycin in extremely obese patients with suspected or confirmed Staphylococcus aureus infections. Pharmacotherapy 35(2):127–139

    Article  CAS  PubMed  Google Scholar 

  • Allard S, Kinzig M, Boivin G et al (1993) Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 54(4):368–373

    Article  CAS  PubMed  Google Scholar 

  • Alobaid AS, Hites M, Lipman J et al (2016) Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review. Int J Antimicrob Agents 47(4):259–268

    Article  CAS  PubMed  Google Scholar 

  • Alquwaizani M, Buckley L, Adams C, Fanikos J (2013) Anticoagulants: a review of the pharmacology, dosing, and complications. Curr Emerg Hosp Med Rep 1:83–97

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson WJ, Lipworth BJ (2012) Does body mass index influence responsiveness to inhaled corticosteroids in persistent asthma? Ann Allergy Asthma Immunol 108(4):237–242

    Article  CAS  PubMed  Google Scholar 

  • Atkinson AJ, Abernethy DR, Daniels CE, Dedrick RL, Markey SP (2007) Principles of clinical pharmacology, 2nd edn. Academic, Amsterdam

    Google Scholar 

  • Bauer LA, Drew Edwards WA, Patchen Dellinger E et al (1983) Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol 24:643–647

    Article  CAS  PubMed  Google Scholar 

  • Beavers CJ, Heron P, Smyth SS et al (2015) Obesity and antiplatelets-does one size fit all? Thromb Res 136:712–716

    Article  CAS  PubMed  Google Scholar 

  • Blouin RA, Warren GW (1999) Pharmacokinetic considerations in obesity. J Pharm Sci 88(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Bordeaux BC, Qayyum R, Yanek LR et al (2010) Effect of obesity on platelet reactivity and response to low-dose aspirin. Prev Cardiol 13:56–62

    Article  CAS  PubMed  Google Scholar 

  • Bowman SL, Hudson SA, Simpson G et al (1986) A comparison of the pharmacokinetics of propranolol in obese and normal volunteers. Br J Clin Pharmacol 21:529–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brill MJ, Diepstraten J, van Rongen A et al (2012) Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 51(5):277–304

    Article  CAS  PubMed  Google Scholar 

  • Brill MJ, van Rongen A, Houwink AP et al (2014a) Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers. Clin Pharmacokinet 53:931–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brill MJ, Houwink AP, Schmidt S et al (2014b) Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. J Antimicrob Chemother 69:715–723

    Article  CAS  PubMed  Google Scholar 

  • Brunton LL, Lazo JS, Parker KL (eds) (2006) Goodman and Gilman’s The pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York

    Google Scholar 

  • Casati A, Putzu M (2005) Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth 17(2):134–145

    Article  CAS  PubMed  Google Scholar 

  • Cataldi M, di Geronimo O, Trio R, Scotti A et al (2016) Utilization of antihypertensive drugs in obesity-related hypertension: a retrospective observational study in a cohort of patients from southern Italy. BMC Pharmacol Toxicol 17:9

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheymol G (2000) Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 39(3):215–231

    Article  CAS  PubMed  Google Scholar 

  • Cheymol G, Poirier J-M, Barre J, Pradalier A, Dry J (1987) Comparative pharmacokinetics of intravenous propranolol in obese and normal volunteers. J Clin Pharmacol 27(11):874–879

    Article  CAS  PubMed  Google Scholar 

  • Cheymol G, Woestenborghs R, Snoeck E et al (1997) Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects. Eur J Clin Pharmacol 51(6):493–498

    Article  CAS  PubMed  Google Scholar 

  • Cho S-J, Yoon I-S, Kim D-D (2013) Obesity-related physiological changes and their pharmacokinetic consequences. J Pharm Investig 43:161–169

    Article  CAS  Google Scholar 

  • Christoff PB, Conti DR, Naylor C, Jusko WJ (1983) Procainamide disposition in obesity. Drug Intell Clin Pharm 17(7–8):516–522

    Article  CAS  PubMed  Google Scholar 

  • de la Peña A, Yeo KP, Linnebjerg H et al (2015) Subcutaneous injection depth does not affect the pharmacokinetics or glucodynamics of insulin lispro in normal weight or healthy obese subjects. J Diabetes Sci Technol 9(4):824–830

    Article  PubMed  PubMed Central  Google Scholar 

  • Dunn TE, Ludwig EA, Slaughter RL et al (1991) Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther 49(5):536–549

    Article  CAS  PubMed  Google Scholar 

  • Dvorchik BH, Damphousse D (2005) The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched non-obese subjects. J Clin Pharmacol 45:48–56

    Article  CAS  PubMed  Google Scholar 

  • Edelman AB, Cherala G, Blue SW et al (2016) Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. Contraception 94(1):52–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan J, de Lannoy IA (2014) Pharmacokinetics. Biochem Pharmacol 87:93–120

    Article  CAS  PubMed  Google Scholar 

  • Farrell GC, Teoh N, McCuskey R (2008) Hepatic microcirculation in fatty liver disease. Anat Rec Adv Integr Anat Evol Biol 291(6):684–692

    Article  Google Scholar 

  • Freeman AL, Pendleton RC, Rondina MT (2010) Prevention of venous thromboembolism in obesity. Expert Rev Cardiovasc Ther 8(12):1711–1721

    Article  PubMed  PubMed Central  Google Scholar 

  • Fukuchi H, Nakashima M, Araki R et al (2009) Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. J Clin Pharm Ther 34(3):329–336

    Article  CAS  PubMed  Google Scholar 

  • Galletti F, Fasano ML, Ferrara LA et al (1989) Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects. J Clin Pharmacol 29(3):212–216

    Article  CAS  PubMed  Google Scholar 

  • Gandhi A, Moorthy B, Ghose R (2012) Drug disposition in pathophysiological conditions. Curr Drug Metab 13(9):1327–1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glasier A (2013) Emergency contraception: clinical outcomes. Contraception 87(3):309–313

    Article  PubMed  Google Scholar 

  • Glasier A, Cameron ST, Blithe D et al (2011) Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception 84(4):363–367

    Article  CAS  PubMed  Google Scholar 

  • Hanley MJ, Abernethy DR, Greenblatt DJ (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 49(2):71–87

    Article  CAS  PubMed  Google Scholar 

  • Hites M, Taccone FS, Wolff F et al (2014) Broad-spectrum β-lactams in obese non-critically ill patients. Nutr Diabetes 4(6):e119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain R, Chung SM, Jain L et al (2011) Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther 90(1):77–89

    Article  CAS  PubMed  Google Scholar 

  • Jensen MD, Ryan DH, Apovian CM et al (2014) 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. J Am Coll Cardiol 63:2985–3023

    Article  PubMed  Google Scholar 

  • Jiang X-L, Samant S, Lesko LJ, Schmidt S (2015) Clinical pharmacokinetics and pharmacodynamics of clopidogrel. Clin Pharmacokinet 54:147–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joy M, Tharp E, Hartman H et al (2016) Safety and efficacy of high-dose unfractionated heparin for prevention of venous thromboembolism in overweight and obese patients. Pharmacotherapy 36(7):740–748

    Article  CAS  PubMed  Google Scholar 

  • Jusko WJ (2017) Clarification of contraceptive drug pharmacokinetics in obesity. Contraception 95:10–16

    Article  CAS  PubMed  Google Scholar 

  • Kees MG, Weber S, Kees F, Horbach T (2011) Pharmacokinetics of moxifloxacin in plasma and tissue of morbidly obese patients. J Antimicrob Chemother 66:2330–2335

    Article  CAS  PubMed  Google Scholar 

  • Knibbe CA, Brill MJ, van Rongen A et al (2015) Drug disposition in obesity: toward evidence-based dosing. Annu Rev Pharmacol Toxicol 55:149–167

    Article  CAS  PubMed  Google Scholar 

  • Kubitza D, Becka M, Zuehlsdorf M, Mueck W (2007) Body weight has limited influence on the safety, tolerability, pharmacokinetics, pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 47:218

    Article  CAS  PubMed  Google Scholar 

  • Landsberg L, Aronne LJ, Beilin LJ et al (2013) Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment. A position paper of the obesity society and the American Society of Hypertension. J Clin Hypertens (Greenwich) 15:14–33

    Article  CAS  Google Scholar 

  • Lentz SR (2016) Thrombosis in the setting of obesity or inflammatory bowel disease. Blood 128(20):2388–2394

    Article  CAS  PubMed  Google Scholar 

  • Levy BI, Schiffrin EL, Mourad JJ et al (2008) Impaired tissue perfusion a pathology common to hypertension, obesity, and diabetes mellitus. Circulation 118(9):968–976

    Article  PubMed  Google Scholar 

  • Leykin Y, Miotto L, Pellis T (2011) Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol 25:27–36

    Article  CAS  PubMed  Google Scholar 

  • Martin JH, Saleem M, Looke D (2012) Therapeutic drug monitoring to adjust dosing in morbid obesity – a new use for an old methodology. Br J Clin Pharmacol 73(5):685–690

    Article  CAS  PubMed  Google Scholar 

  • Michalaki MA, Gkotsina MI, Mamali I et al (2011) Impaired pharmacokinetics of levothyroxine in severely obese volunteers. Thyroid 21(5):477–481

    Article  CAS  PubMed  Google Scholar 

  • Moine P, Mueller SW, Schoen JA et al (2016) Pharmacokinetic and pharmacodynamic evaluation of a weight-based dosing regimen of cefoxitin for perioperative surgical prophylaxis in obese and morbidly obese patients. Antimicrob Agents Chemother 60(10):5885–5893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mornar S, Chan LN, Mistretta S et al (2012) Pharmacokinetics of the etonogestrel contraceptive implant in obese women. Am J Obstet Gynecol 207(2):110.e1–110.e6

    Article  CAS  Google Scholar 

  • Morrish GA, Pai MP, Green B (2011) The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol 7(6):697–706

    Article  CAS  PubMed  Google Scholar 

  • Mueck W, Stampfuss J, Kubitza D, Becka M (2014) Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet 53:1–16

    Article  CAS  PubMed  Google Scholar 

  • Munjal S, Gautam A, Rapoport AM, Fisher DM (2016) The effect of weight, body mass index, age, sex, and race on plasma concentrations of subcutaneous sumatriptan: a pooled analysis. Clin Pharmacol Adv Appl 8:109–116

    CAS  Google Scholar 

  • Reflection paper on investigation of pharmacokinetics and pharmacodynamics in the obese population 25 January 2018 1, EMA/CHMP/535116/2016 2, Committee for Human Medicinal Products (CHMP)

    Google Scholar 

  • Robinson JA, Burke AE (2013) Obesity and hormonal contraceptive efficacy. Women’s Health (Lond Engl) 9(5):453–466

    Article  CAS  Google Scholar 

  • Rowland M, Tozer TN (1995) Clinical pharmacokinetics, concepts and applications, 3rd edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Shah DK, Missmer SA, Correia KF, Ginsburg ES (2014) Pharmacokinetics of human chorionic gonadotropin injection in obese and normal-weight women. J Clin Endocrinol Metab 99(4):1314–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shank BR, Zimmerman DE (2015) Demystifying drug dosing in obese patients. American Society of Health System Pharmacists. eBook

    Google Scholar 

  • Simmons KB, Edelman AB (2016) Hormonal contraception and obesity. Fertil Steril 106(6):1282–1288

    Article  CAS  PubMed  Google Scholar 

  • Smit C, De Hoogd S, Brüggemann RJM, Knibbe CAJ (2018) Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol 14(3):275–285

    Article  CAS  PubMed  Google Scholar 

  • Steinkampf MP, Hammond KR, Nichols JE, Slayden SH (2003) Effect of obesity on recombinant follicle stimulating hormone absorption: subcutaneous versus intramuscular administration. Fertil Steril 80(1):99–102

    Article  PubMed  Google Scholar 

  • Sturm AW, Allen N, Rafferty KD et al (2014) Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Pharmacotherapy 34(1):28–35

    Article  CAS  PubMed  Google Scholar 

  • Thompson-Moore NR, Wanat MA, Putney DR et al (2015) Evaluation and pharmacokinetics of treatment dose enoxaparin in hospitalized patients with morbid obesity. Clin Appl Thromb Hemost 21(6):513–520

    Article  CAS  PubMed  Google Scholar 

  • Tucker GT (1981) Measurement of the renal clearance of drugs. Br J Clin Pharmacol 12:761–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Kralingen S, Diepstraten J, Peeters MY et al (2011) Population pharmacokinetics and pharmacodynamics of propofol in morbidly obese patients. Clin Pharmacokinet 50:739–750

    Article  PubMed  Google Scholar 

  • van Rongen A, Välitalo PAJ, Peeters MYM et al (2016) Morbidly obese patients exhibit increased CYP2E1-mediated oxidation of acetaminophen. Clin Pharmacokinet 55:833–847

    Article  PubMed  PubMed Central  Google Scholar 

  • Wallace JL, Reaves AB, Tolley EA et al (2013) Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 36(1):96–101

    Article  CAS  PubMed  Google Scholar 

  • Westhoff CL, Reinecke I, Bangerter K, Merz M (2014) Impact of body mass index on suppression of follicular development and ovulation using a transdermal patch containing 0.55-mg ethinyl estradiol/2.1-mg gestodene: a multicenter, open-label, uncontrolled study over three treatment cycles. Contraception 90(3):272–279

    Article  CAS  PubMed  Google Scholar 

  • Wójcicki J, Jaroszynska M, Droździk M et al (2003) Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects. Biopharm Drug Dispos 24(5):211–218

    Article  PubMed  Google Scholar 

  • World Health Organization (2018) Obesity and overweight. http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 8 Oct 2018

  • Wu B (2016) Morbid obesity alters both pharmacokinetics and pharmacodynamics of propofol: dosing recommendation for anesthesia induction (Short communication). Drug Metab Dispos 44:1579–1583

    Article  PubMed  Google Scholar 

  • Zuckerman M, Greller HA, Babu KM (2015) A review of the toxicologic implications of obesity. J Med Toxicol 11:342–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular and Metabolism Medical Affairs, Janssen Pharmaceuticals Inc., Titusville, NJ, USA

    Kenneth T. Moore

Authors
  1. Kenneth T. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth T. Moore .

Editor information

Editors and Affiliations

  1. CorDynamics , Dieburg, Germany

    Franz J. Hock

  2. CorDynamics , Chicago, IL, USA

    Michael R. Gralinski

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Moore, K.T. (2019). Special Populations: Profiling the Effect of Obesity on Drug Disposition and Pharmacodynamics. In: Hock, F., Gralinski, M. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_7-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-56637-5_7-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56637-5

  • Online ISBN: 978-3-319-56637-5

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation