Journal of Medical Toxicology

, Volume 11, Issue 3, pp 342–354 | Cite as

A Review of the Toxicologic Implications of Obesity

  • Matthew ZuckermanEmail author
  • Howard A Greller
  • Kavita M Babu
Review Article


The increasing prevalence of obesity in developed nations has far-reaching implications for medical toxicology. The management of obese patients is complicated by comorbid illnesses, changes in cardiovascular and respiratory physiology, alterations in pharmacokinetics, and a lack of studies to identify appropriate dosing for current therapeutics and antidotes. In this review article, we examine obesity-associated physiologic and pharmacokinetic changes that may increase the vulnerability of obese patients to overdose. Further research is needed to characterize the relationship between drug toxicity and obesity.


Obesity Toxicology Pharmacokinetics Antidotes 



The authors have no funding to report in relation to this study.

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Freedman DS, CDC. Obesity—United States, 1988–2008. MMWR Surveill Summ. 2011;60(Suppl):73–7.PubMedGoogle Scholar
  2. 2.
    May AL, Freedman D, Sherry B, Blanck HM, CDC. Obesity—United States, 1999–2010. MMWR Surveill Summ. 2013;62 Suppl 3:120–8.PubMedGoogle Scholar
  3. 3.
    Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985–3023. doi: 10.1016/j.jacc.2013.11.004.PubMedCrossRefGoogle Scholar
  4. 4.
    Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1–253.Google Scholar
  5. 5.
    Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Am J Clin Nutr. 1998;68(4):899–917.Google Scholar
  6. 6.
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311(8):806–14. doi: 10.1001/jama.2014.732.PubMedCrossRefGoogle Scholar
  7. 7.
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief. 2012;(82):1–8.Google Scholar
  8. 8.
    NCHS. Health, United States, 2012: with special feature on emergency care. Hyattsville, Maryland; 2013.Google Scholar
  9. 9.
    Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563–70. doi: 10.1016/j.amepre.2011.10.026.PubMedCrossRefGoogle Scholar
  10. 10.
    Hill JO. Environmental contributions to the obesity epidemic. Science. 1998;280(5368):1371–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Cutler D, Glaeser E, Shapiro J. Why have Americans become more obese? J Econ Perspect. 2003;17(3):93–118.CrossRefGoogle Scholar
  12. 12.
    Du H, Feskens E. Dietary determinants of obesity. Acta Cardiol. 2010;65(4):377–86.PubMedGoogle Scholar
  13. 13.
    Mitchell JA, Byun W. Sedentary behavior and health outcomes in children and adolescents. Am J Lifestyle Med. 2013. doi: 10.1177/1559827613498700.Google Scholar
  14. 14.
    McVinnie DS. Obesity and pain. Br J Pain. 2013;7(4):163–70.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Health implications of obesity. National Institutes of Health Consensus Development Conference Statement. Ann Intern Med. 1985;103(1):147–51.Google Scholar
  16. 16.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38. doi: 10.1056/NEJMoa021423.PubMedCrossRefGoogle Scholar
  17. 17.
    Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71–82. doi: 10.1001/jama.2012.113905.PubMedCrossRefGoogle Scholar
  18. 18.
    Mack KA, CDC. Drug-induced deaths—United States, 1999–2010. MMWR Surveill Summ. 2013;62 Suppl 3:161–3.PubMedGoogle Scholar
  19. 19.
    Lemmens HJ, Bernstein DP, Brodsky JB. Estimating blood volume in obese and morbidly obese patients. Obes Surg. 2006;16(6):773–6. doi: 10.1381/096089206777346673.PubMedCrossRefGoogle Scholar
  20. 20.
    Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci. 2001;321(4):225–36.PubMedCrossRefGoogle Scholar
  21. 21.
    Ferraro S, Perrone-Filardi P, Desiderio A, Betocchi S, D’Alto M, Liguori L, et al. Left ventricular systolic and diastolic function in severe obesity: a radionuclide study. Cardiology. 1996;87(4):347–53.PubMedCrossRefGoogle Scholar
  22. 22.
    Lee JF, Harrison ML, Christmas KM, Kim K, Hurr C, Brothers RM. Elevated resting heart rate and reduced orthostatic tolerance in obese humans. Clin Auton Res. 2013. doi: 10.1007/s10286-013-0222-x.Google Scholar
  23. 23.
    Stamler R, Stamler J, Riedlinger WF, Algera G, Roberts RH. Weight and blood pressure. Findings in hypertension screening of 1 million Americans. JAMA. 1978;40(15):1607–10.CrossRefGoogle Scholar
  24. 24.
    Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113(6):898–918. doi: 10.1161/CIRCULATIONAHA.106.171016.PubMedCrossRefGoogle Scholar
  25. 25.
    Strandgaard S, Andersen GS, Ahlgreen P, Nielsen PE. Visual disturbances and occipital brain infarct following acute, transient hypotension in hypertensive patients. Acta Med Scand. 1984;216(4):417–22.PubMedCrossRefGoogle Scholar
  26. 26.
    McLaren GD, Danta G. Cerebral infarction due to presumed haemodynamic factors in ambulant hypertensive patients. Clin Exp Neurol. 1987;23:55–66.PubMedGoogle Scholar
  27. 27.
    Honiden S. Caring for the critically ill, obese patient. PCCSU; 2011.Google Scholar
  28. 28.
    Wang D, Teichtahl H. Opioids, sleep architecture and sleep-disordered breathing. Sleep Med Rev. 2007;11(1):35–46. doi: 10.1016/j.smrv.2006.03.006.PubMedCrossRefGoogle Scholar
  29. 29.
    Mogri M, Desai H, Webster L, Grant BJ, Mador MJ. Hypoxemia in patients on chronic opiate therapy with and without sleep apnea. Sleep Breath. 2009;13(1):49–57. doi: 10.1007/s11325-008-0208-4.PubMedCrossRefGoogle Scholar
  30. 30.
    Harris AT, Morell D, Bajaj Y, Martin-Hirsch DP. A discussion of airway and respiratory complications along with general considerations in obese patients. Int J Clin Pract. 2010;64(6):802–6. doi: 10.1111/j.1742-1241.2010.02350.x.PubMedCrossRefGoogle Scholar
  31. 31.
    Ramachandran SK, Haider N, Saran KA, Mathis M, Kim J, Morris M, et al. Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy. J Clin Anesth. 2011;23(3):207–13. doi: 10.1016/j.jclinane.2010.09.003.PubMedCrossRefGoogle Scholar
  32. 32.
    Mushref MA, Srinivasan S. Effect of high fat-diet and obesity on gastrointestinal motility. Ann Transl Med. 2013;1(2):14. doi: 10.3978/j.issn.2305-5839.2012.11.01.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Cardoso-Junior A, Coelho LG, Savassi-Rocha PR, Vignolo MC, Abrantes MM, de Almeida AM, et al. Gastric emptying of solids and semi-solids in morbidly obese and non-obese subjects: an assessment using the 13C-octanoic acid and 13C-acetic acid breath tests. Obes Surg. 2007;17(2):236–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Acosta A, Camilleri M, Shin A, Vazquez-Roque MI, Iturrino J, Burton D, et al. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology. 2015;148(3):537–46 e4. doi: 10.1053/j.gastro.2014.11.020.
  35. 35.
    Wright RA, Krinsky S, Fleeman C, Trujillo J, Teague E. Gastric emptying and obesity. Gastroenterology. 1983;84(4):747–51.PubMedGoogle Scholar
  36. 36.
    Jackson SJ, Leahy FE, McGowan AA, Bluck LJ, Coward WA, Jebb SA. Delayed gastric emptying in the obese: an assessment using the non-invasive (13)C-octanoic acid breath test. Diabetes Obes Metab. 2004;6(4):264–70. doi: 10.1111/j.1462-8902.2004.0344.x.PubMedCrossRefGoogle Scholar
  37. 37.
    Horowitz M, Collins PJ, Cook DJ, Harding PE, Shearman DJ. Abnormalities of gastric emptying in obese patients. Int J Obes. 1983;7(5):415–21.PubMedGoogle Scholar
  38. 38.
    Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes Rev. 2004;5(1):27–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Cikim AS, Topal E, Harputluoglu M, Keskin L, Zengin Z, Cikim K, et al. Epicardial adipose tissue, hepatic steatosis and obesity. J Endocrinol Investig. 2007;30(6):459–64.CrossRefGoogle Scholar
  40. 40.
    Buechler C, Weiss TS. Does hepatic steatosis affect drug metabolizing enzymes in the liver? Curr Drug Metab. 2011;12(1):24–34.PubMedCrossRefGoogle Scholar
  41. 41.
    Pan A, Sun Q, Czernichow S, Kivimaki M, Okereke OI, Lucas M, et al. Bidirectional association between depression and obesity in middle-aged and older women. Int J Obes (Lond). 2012;36(4):595–602. doi: 10.1038/ijo.2011.111.CrossRefGoogle Scholar
  42. 42.
    Dixon JB, Dixon ME, O’Brien PE. Depression in association with severe obesity: changes with weight loss. Arch Intern Med. 2003;163(17):2058–65. doi: 10.1001/archinte.163.17.2058.PubMedCrossRefGoogle Scholar
  43. 43.
    McElroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE, Nemeroff CB. Are mood disorders and obesity related? A review for the mental health professional. J Clin Psychiatry. 2004;65(5):634–51, quiz 730.Google Scholar
  44. 44.
    Alcaro A, Panksepp J. The SEEKING mind: primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression. Neurosci Biobehav Rev. 2011;35(9):1805–20. doi: 10.1016/j.neubiorev.2011.03.002.PubMedCrossRefGoogle Scholar
  45. 45.
    Wang GJ, Volkow ND, Thanos PK, Fowler JS. Imaging of brain dopamine pathways: implications for understanding obesity. J Addict Med. 2009;3(1):8–18. doi: 10.1097/ADM.0b013e31819a86f7.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Baik JH. Dopamine signaling in reward-related behaviors. Front Neural Circ. 2013;7:152. doi: 10.3389/fncir.2013.00152.Google Scholar
  47. 47.
    Bluml V, Kapusta N, Vyssoki B, Kogoj D, Walter H, Lesch OM. Relationship between substance use and body mass index in young males. Am J Addict. 2012;21(1):72–7. doi: 10.1111/j.1521-0391.2011.00192.x.PubMedCrossRefGoogle Scholar
  48. 48.
    Gearhardt AN, Harrison EL, McKee SA. Does co-morbid depression alter the inverse relationship between obesity and substance use disorders? Drug Alcohol Depend. 2012;124(1–2):185–8. doi: 10.1016/j.drugalcdep.2012.01.002.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Hitt HC, McMillen RC, Thornton-Neaves T, Koch K, Cosby AG. Comorbidity of obesity and pain in a general population: results from the Southern Pain Prevalence Study. J Pain. 2007;8(5):430–6. doi: 10.1016/j.jpain.2006.12.003.PubMedCrossRefGoogle Scholar
  50. 50.
    Counterweight Project Team. The impact of obesity on drug prescribing in primary care. Br J Gen Pract. 2005;55(519):743–9.PubMedCentralGoogle Scholar
  51. 51.
    Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85–92. doi: 10.7326/0003-4819-152-2-201001190-00006.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Manchikanti L, Helm S, Fellows B, Janata JW, Pampati V, Grider JS, et al. Opioid epidemic in the United States. Pain Phys. 2012;15(3 Suppl):ES9–38.Google Scholar
  53. 53.
    Han PY, Duffull SB, Kirkpatrick CM, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007;82(5):505–8. doi: 10.1038/sj.clpt.6100381.PubMedCrossRefGoogle Scholar
  54. 54.
    Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71–87. doi: 10.2165/11318100-000000000-00000.PubMedCrossRefGoogle Scholar
  55. 55.
    Leykin Y, Miotto L, Pellis T. Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol. 2011;25(1):27–36.PubMedCrossRefGoogle Scholar
  56. 56.
    Du BD, Du BE. Clinical calorimetry: tenth paper a formula to estimate the approximate surface area if height and weight be known. Arch Intern Med. 1916;XVII(6_2):863–71. doi: 10.1001/archinte.1916.00080130010002.CrossRefGoogle Scholar
  57. 57.
    Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098. doi: 10.1056/NEJM198710223171717.PubMedGoogle Scholar
  58. 58.
    Lopes-Serrao MD, Ussery SM, Hall RG, Shah SR. Evaluation of chemotherapy-induced severe myelosuppression incidence in obese patients with capped dosing. J Oncol Pract. 2011;7(1):13–7. doi: 10.1200/JOP.2010.000045.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2012;30(13):1553–61. doi: 10.1200/JCO.2011.39.9436.PubMedCrossRefGoogle Scholar
  60. 60.
    Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39(3):215–31. doi: 10.2165/00003088-200039030-00004.PubMedCrossRefGoogle Scholar
  61. 61.
    Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004;58(2):119–33. doi: 10.1111/j.1365-2125.2004.02157.x.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage. Implications for drug therapy. Clin Pharmacokinet. 1994;26(4):292–307. doi: 10.2165/00003088-199426040-00005.PubMedCrossRefGoogle Scholar
  63. 63.
    Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051–65. doi: 10.2165/00003088-200544100-00004.PubMedCrossRefGoogle Scholar
  64. 64.
    De Baerdemaeker LE, Mortier EP, Struys MM. Pharmacokinetics in obese patients. Contin Educ Anaesth Crit Care Pain. 2004;4(5):152–5. doi: 10.1093/bjaceaccp/mkh042.CrossRefGoogle Scholar
  65. 65.
    Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth. 2005;17(2):134–45. doi: 10.1016/j.jclinane.2004.01.009.PubMedCrossRefGoogle Scholar
  66. 66.
    Lloret Linares C, Decleves X, Oppert JM, Basdevant A, Clement K, Bardin C, et al. Pharmacology of morphine in obese patients: clinical implications. Clin Pharmacokinet. 2009;48(10):635–51. doi: 10.2165/11317150-000000000-00000.PubMedCrossRefGoogle Scholar
  67. 67.
    Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth. 2010;105 Suppl 1:i16–23. doi: 10.1093/bja/aeq312.PubMedCrossRefGoogle Scholar
  68. 68.
    Alsio A, Rembeck K, Askarieh G, Christensen PB, Farkkila M, Langeland N, et al. Impact of obesity on the bioavailability of peginterferon-alpha2a and ribavirin and treatment outcome for chronic hepatitis C genotype 2 or 3. PLoS ONE. 2012;7(5), e37521. doi: 10.1371/journal.pone.0037521.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Diepstraten J, Chidambaran V, Sadhasivam S, Esslinger HR, Cox SL, Inge TH, et al. Propofol clearance in morbidly obese children and adolescents: influence of age and body size. Clin Pharmacokinet. 2012;51(8):543–51. doi: 10.2165/11632940-000000000-00000.PubMedCrossRefGoogle Scholar
  70. 70.
    Mornar S, Chan LN, Mistretta S, Neustadt A, Martins S, Gilliam M. Pharmacokinetics of the etonogestrel contraceptive implant in obese women. Am J Obstet Gynecol. 2012;207(2):110 e1-6. doi: 10.1016/j.ajog.2012.05.002.
  71. 71.
    Blouin RA, Warren GW. Pharmacokinetic considerations in obesity. J Pharm Sci. 1999;88(1):1–7. doi: 10.1021/js980173a.PubMedCrossRefGoogle Scholar
  72. 72.
    Kolka CM, Harrison LN, Lottati M, Chiu JD, Kirkman EL, Bergman RN. Diet-induced obesity prevents interstitial dispersion of insulin in skeletal muscle. Diabetes. 2010;59(3):619–26. doi: 10.2337/db09-0839.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Sindelka G, Heinemann L, Berger M, Frenck W, Chantelau E. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. Diabetologia. 1994;37(4):377–80.PubMedCrossRefGoogle Scholar
  74. 74.
    Vora JP, Burch A, Peters JR, Owens DR. Relationship between absorption of radiolabeled soluble insulin, subcutaneous blood flow, and anthropometry. Diabetes Care. 1992;15(11):1484–93.PubMedCrossRefGoogle Scholar
  75. 75.
    Dayananda L, Belaval VV, Raina A, Chandana R. Intended intramuscular gluteal injections: are they truly intramuscular? J Postgrad Med. 2014;60(2):175–8. doi: 10.4103/0022-3859.132334.PubMedCrossRefGoogle Scholar
  76. 76.
    Chantel S, Martin P, Petit P, Massignon D, Dode X, Maire P, et al. Pharmacokinetic variability of the absorption of enoxaparin used subcutaneously for venous thromboembolism prophylaxis. Population Approach Group Europe; 2006.Google Scholar
  77. 77.
    Livingston EH. The incidence of bariatric surgery has plateaued in the U.S. Am J Surg. 2010;200(3):378–85. doi: 10.1016/j.amjsurg.2009.11.007.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Edwards A, Ensom MH. Pharmacokinetic effects of bariatric surgery. Ann Pharmacother. 2012;46(1):130–6. doi: 10.1345/aph.1Q414.PubMedCrossRefGoogle Scholar
  79. 79.
    Braghetto I, Davanzo C, Korn O, Csendes A, Valladares H, Herrera E, et al. Scintigraphic evaluation of gastric emptying in obese patients submitted to sleeve gastrectomy compared to normal subjects. Obes Surg. 2009;19(11):1515–21. doi: 10.1007/s11695-009-9954-z.PubMedCrossRefGoogle Scholar
  80. 80.
    Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010;11(1):41–50. doi: 10.1111/j.1467-789X.2009.00614.x.PubMedCrossRefGoogle Scholar
  81. 81.
    Olson K. Poisoning and drug overdose. 6th ed. New York: McGraw-Hill Education; 2007.Google Scholar
  82. 82.
    Corcoran GB, Salazar DE. Obesity as a risk factor in drug-induced organ injury. IV. Increased gentamicin nephrotoxicity in the obese overfed rat. J Pharmacol Exp Ther. 1989;248(1):17–22.PubMedGoogle Scholar
  83. 83.
    Schwartz AE, Matteo RS, Ornstein E, Young WL, Myers KJ. Pharmacokinetics of sufentanil in obese patients. Anesth Analg. 1991;73(6):790–3.PubMedGoogle Scholar
  84. 84.
    Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, et al. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology. 1998;89(3):562–73.PubMedCrossRefGoogle Scholar
  85. 85.
    Leykin Y, Pellis T, Lucca M, Lomangino G, Marzano B, Gullo A. The effects of cisatracurium on morbidly obese women. Anesth Analg. 2004;99(4):1090–4. doi: 10.1213/01.ANE.0000132781.62934.37.PubMedCrossRefGoogle Scholar
  86. 86.
    Leykin Y, Pellis T, Lucca M, Lomangino G, Marzano B, Gullo A. The pharmacodynamic effects of rocuronium when dosed according to real body weight or ideal body weight in morbidly obese patients. Anesth Analg. 2004;99(4):1086–9. doi: 10.1213/01.ANE.0000120081.99080.C2.PubMedCrossRefGoogle Scholar
  87. 87.
    Sparreboom A, Wolff AC, Mathijssen RH, Chatelut E, Rowinsky EK, Verweij J, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol. 2007;25(30):4707–13. doi: 10.1200/JCO.2007.11.2938.PubMedCrossRefGoogle Scholar
  88. 88.
    Allard S, Kinzig M, Boivin G, Sorgel F, LeBel M. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther. 1993;54(4):368–73.PubMedCrossRefGoogle Scholar
  89. 89.
    Taivainen T, Tuominen M, Rosenberg PH. Influence of obesity on the spread of spinal analgesia after injection of plain 0.5% bupivacaine at the L3-4 or L4-5 interspace. Br J Anaesth. 1990;64(5):542–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Hogan QH, Prost R, Kulier A, Taylor ML, Liu S, Mark L. Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and abdominal pressure. Anesthesiology. 1996;84(6):1341–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Ellero S, Chakhtoura G, Barreau C, Langouet S, Benelli C, Penicaud L, et al. Xenobiotic-metabolizing cytochromes p450 in human white adipose tissue: expression and induction. Drug Metab Dispos. 2010;38(4):679–86. doi: 10.1124/dmd.109.029249.PubMedCrossRefGoogle Scholar
  92. 92.
    Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51(5):277–304. doi: 10.2165/11599410-000000000-00000.PubMedCrossRefGoogle Scholar
  93. 93.
    Snawder JE, Roe AL, Benson RW, Roberts DW. Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity. Biochem Biophys Res Commun. 1994;203(1):532–9. doi: 10.1006/bbrc.1994.2215.PubMedCrossRefGoogle Scholar
  94. 94.
    Murphy R, Swartz R, Watkins PB. Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med. 1990;113(10):799–800.PubMedCrossRefGoogle Scholar
  95. 95.
    Abernethy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum. 1985;28(10):1117–21.PubMedCrossRefGoogle Scholar
  96. 96.
    Abernethy DR, Divoll M, Greenblatt DJ, Ameer B. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther. 1982;31(6):783–90.PubMedCrossRefGoogle Scholar
  97. 97.
    Abernethy DR, Greenblatt DJ, Divoll M, Shader RI. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med. 1983;101(6):873–80.PubMedGoogle Scholar
  98. 98.
    Bentley JB, Borel JD, Vaughan RW, Gandolfi AJ. Weight, pseudocholinesterase activity, and succinylcholine requirement. Anesthesiology. 1982;57(1):48–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Tanaka E, Yamazaki K, Misawa S. Update: the clinical importance of acetaminophen hepatotoxicity in non-alcoholic and alcoholic subjects. J Clin Pharm Ther. 2000;25(5):325–32.PubMedCrossRefGoogle Scholar
  100. 100.
    Vuilleumier N, Rossier MF, Chiappe A, Degoumois F, Dayer P, Mermillod B, et al. CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis. Eur J Clin Pharmacol. 2006;62(6):423–9. doi: 10.1007/s00228-006-0111-5.PubMedCrossRefGoogle Scholar
  101. 101.
    Salazar DE, Schentag JJ, Corcoran GB. Obesity as a risk factor in drug-induced organ injury. V. Toxicokinetics of gentamicin in the obese overfed rat. Drug Metab Dispos. 1992;20(3):402–6.PubMedGoogle Scholar
  102. 102.
    Jesudason DR, Clifton P. Interpreting different measures of glomerular filtration rate in obesity and weight loss: pitfalls for the clinician. Int J Obes (Lond). 2012;36:1421–7. doi: 10.1038/ijo.2011.242.CrossRefGoogle Scholar
  103. 103.
    Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347(5):305–13. doi: 10.1056/NEJMoa020245.PubMedCrossRefGoogle Scholar
  104. 104.
    Abrass CK. Overview: Obesity: what does it have to do with kidney disease? J Am Soc Nephrol. 2004;15(11):2768–72. doi: 10.1097/01.ASN.0000141963.04540.3E.PubMedCrossRefGoogle Scholar
  105. 105.
    Lavie CJ, Mehra MR, Milani RV. Obesity and heart failure prognosis: paradox or reverse epidemiology? Eur Heart J. 2005;26(1):5–7. doi: 10.1093/eurheartj/ehi055.PubMedCrossRefGoogle Scholar
  106. 106.
    Praga M. Obesity—a neglected culprit in renal disease. Nephrol Dial Transplant. 2002;17:1157–9.PubMedCrossRefGoogle Scholar
  107. 107.
    Amann K, Benz K. Structural renal changes in obesity and diabetes. Semin Nephrol. 2013;33:23–33. doi: 10.1016/j.semnephrol.2012.12.003.PubMedCrossRefGoogle Scholar
  108. 108.
    Penzak SR, Gubbins PO, Rodvold KA, Hickerson SL. Therapeutic drug monitoring of vancomycin in a morbidly obese patient. Ther Drug Monit. 1998;20:261–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med. 1988;84(6):1053–60.PubMedCrossRefGoogle Scholar
  110. 110.
    Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.PubMedCrossRefGoogle Scholar
  111. 111.
    Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. 2012;32(7):604–12. doi: 10.1002/j.1875-9114.2012.01098.x.PubMedCrossRefGoogle Scholar
  112. 112.
    Cho S-J, Yoon I-S, Kim D-D. Obesity-related physiological changes and their pharmacokinetic consequences. J Pharm Investig. 2013;43(3):161–9. doi: 10.1007/s40005-013-0073-4.CrossRefGoogle Scholar
  113. 113.
    McLeay SC, Morrish GA, Kirkpatrick CM, Green B. The relationship between drug clearance and body size: systematic review and meta-analysis of the literature published from 2000 to 2007. Clin Pharmacokinet. 2012;51(5):319–30. doi: 10.2165/11598930-000000000-00000.PubMedCrossRefGoogle Scholar
  114. 114.
    Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998;54:621–5.PubMedCrossRefGoogle Scholar
  115. 115.
    Dvorchik BH, Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol. 2005;45:48–56. doi: 10.1177/0091270004269562.PubMedCrossRefGoogle Scholar
  116. 116.
    Pai MP, Norenberg JP, Anderson T, Goade DW, Rodvold KA, Telepak RA, et al. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007;51:2741–7. doi: 10.1128/AAC.00059-07.PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Yee JY, Duffull SB. The effect of body weight on dalteparin pharmacokinetics. A preliminary study. Eur J Clin Pharmacol. 2000;56:293–7.PubMedCrossRefGoogle Scholar
  118. 118.
    Barras MA, Duffull SB, Atherton JJ, Green B. Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events. Br J Clin Pharmacol. 2009;68:700–11. doi: 10.1111/j.1365-2125.2009.03518.x.PubMedCentralPubMedCrossRefGoogle Scholar
  119. 119.
    Willett KC, Alsharhan M, Durand C, Cooper MR. Dosing of enoxaparin for venous thromboembolism prophylaxis in obese patients. Ann Pharmacother. 2013;47:1717–20. doi: 10.1177/1060028013507902.PubMedCrossRefGoogle Scholar
  120. 120.
    Bauer LA, Wareing-Tran C, Edwards WA, Raisys V, Ferreri L, Jack R, et al. Cimetidine clearance in the obese. Clin Pharmacol Ther. 1985;37:425–30.PubMedCrossRefGoogle Scholar
  121. 121.
    Abernethy DR, Greenblatt DJ, Matlis R, Gugler R. Cimetidine disposition in obesity. Am J Gastroenterol. 1984;79:91–4.PubMedGoogle Scholar
  122. 122.
    Chyka PA, Seger D, Krenzelok EP, Vale JA, AACT, EAPCCT. Position paper: single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61–87.CrossRefGoogle Scholar
  123. 123.
    McNamara RM, Aaron CK, Gemborys M, Davidheiser S. Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose. Ann Emerg Med. 1989;18(9):934–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1999;37(6):731–51.Google Scholar
  125. 125.
    Krag E, Hojgaard L. Bile acid metabolism after intestinal bypass operations. Int J Obes. 1981;5(5):519–25.PubMedGoogle Scholar
  126. 126.
    Dunning K, Plymyer MR. Charcoal peritonitis causing chronic pelvic pain: a unique complication following bariatric surgery. Obes Surg. 2006;16(9):1238–42. doi: 10.1381/096089206778392121.PubMedCrossRefGoogle Scholar
  127. 127.
    Van Dinter Jr TG, John L, Guileyardo JM, John SF. Intestinal perforation caused by insertion of a nasogastric tube late after gastric bypass. Proc (Baylor Univ Med Cent). 2013;26(1):11–5.Google Scholar
  128. 128.
    Appelboam AV, Dargan PI, Knighton J. Fatal anaphylactoid reaction to N-acetylcysteine: caution in patients with asthma. Emerg Med J. 2002;19(6):594–5.PubMedCentralPubMedCrossRefGoogle Scholar
  129. 129.
    Prizont R. Medical officer review: acetadote. FDA Center for Drug Evaluation and Research: Office of Drug Evaluation. 2003. Accessed 16 May 2015.
  130. 130.
    Duncan R, Cantlay G, Paterson B. New recommendation for N-acetylcystiene dosing may reduce incidence of adverse effects. Emerg Med J. 2006;23(7):584. doi: 10.1136/emj.2005.031104.PubMedCentralPubMedCrossRefGoogle Scholar
  131. 131.
    Intralipid [package insert]. Deerfield: Baxter Healthare Corporation; 2007.Google Scholar
  132. 132.
    Methylene blue [package insert]. Lake Forest: Akorn, Inc.; 2008.Google Scholar
  133. 133.
    El-Solh A, Sikka P, Bozkanat E, Jaafar W, Davies J. Morbid obesity in the medical ICU. Chest. 2001;120(6):1989–97.PubMedCrossRefGoogle Scholar
  134. 134.
    Akinnusi ME, Pineda LA, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta-analysis. Crit Care Med. 2008;36(1):151–8. doi: 10.1097/01.CCM.0000297885.60037.6E.PubMedCrossRefGoogle Scholar
  135. 135.
    Bercault N, Boulain T, Kuteifan K, Wolf M, Runge I, Fleury JC. Obesity-related excess mortality rate in an adult intensive care unit: a risk-adjusted matched cohort study. Crit Care Med. 2004;32(4):998–1003.PubMedCrossRefGoogle Scholar
  136. 136.
    Tremblay A, Bandi V. Impact of body mass index on outcomes following critical care. Chest. 2003;123(4):1202–7.PubMedCrossRefGoogle Scholar

Copyright information

© American College of Medical Toxicology 2015

Authors and Affiliations

  • Matthew Zuckerman
    • 1
    Email author
  • Howard A Greller
    • 2
    • 3
  • Kavita M Babu
    • 4
  1. 1.University of ColoradoAuroraUSA
  2. 2.Icahn School of Medicine at Mount SinaiNew York CityUSA
  3. 3.Department of Emergency MedicineIcahn School of Medicine at Mount SinaiNew York CityUSA
  4. 4.Division of Medical Toxicology, Department of Emergency MedicineUMass Memorial Medical CenterWorcesterUSA

Personalised recommendations