Abstract
The purpose of this paper is to provide clinicians with important considerations and caveats when evaluating published literature on medication dosing in obese subjects, since much of this literature involves short-term pharmacokinetic or pharmacodynamic studies that are not designed to look at clinically important outcomes. A secondary objective is to suggest improvements in the reporting of dosing information derived from clinical studies and incorporated into product information labeling that should help clinicians design medication-specific dosing regimens for patients with obesity. Data sources included published studies, review papers, and clinical practice guidelines concerning drug dosing of subjects with obesity. Medication dosing recommendations in product labeling typically are derived from studies of normal healthy volunteers and patients with single-system disease states or patients in a specialized setting (e.g. operating room, intensive care unit). Even in studies with relatively large sample sizes there are often relatively few subjects with extremes of body composition such as patients with a body mass index (BMI) greater than 40 kg/m2, so the appropriateness of labeled dosing information for these subjects is particularly ill-defined. Investigations of medication labeling information have demonstrated the inadequacy of this information for dosing patients of more extreme body size. Clinical investigations of drugs should be designed and the results reported in a manner that allows for meaningful recommendations for drug dosing in patients with varying degrees of obesity. Until and when such studies are routinely performed, there are steps that can be taken by the pharmaceutical industry, clinicians, and governmental agencies to help insure optimal drug dosing in obesity.
Similar content being viewed by others
References
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311:806–14.
Centers for Disease Control and Prevention: Data, Trends and Maps. Available online at: http://www.cdc.gov/obesity/data/prevalence-maps.html. Accessed 13 Jan 2016.
Centers for Disease Control and Prevention: NCHS Health E-Stat. Available online at: http://www.cdc.gov/nchs/data/hestat/obesity_adult_09_10/obesity_adult_09_10.htm. Accessed 13 Jan 2016.
Godoy R, Goodman E, Levins R, Leonard WR. Anthropometric variability in the USA: 1971–2002. Ann Hum Biol. 2005;32:469–86.
Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer and service-specific estimates. Health Aff. 2009;28:w822–31.
Grieve E, Fenwick E, Yang H-C, Lean M. The disproportionate economic burden associated with severe and complicated obesity: a systematic review. Obesity Rev. 2013;14:883–94.
Van Lancker P1, Dillemans B, Bogaert T, Mulier JP, De Kock M, Haspeslagh M. Ideal versus corrected body weight for dosage of sugammadex in morbidly obese patients. Anaesthesia 2011;66:721–5.
van Kralingen S, van de Garde EM, Knibbe CA, Diepstraten J, Wiezer MJ, van Ramshorst B, van Dongen EP. Comparative evaluation of atracurium dosed on ideal body weight vs. total body weight in morbidly obese patients. Br J Clin Pharmacol 2011;71:34–40.
Ingrande J, Brodsky JB, Lemmens HJ. Lean body weight scalar for the anesthetic induction dose of propofol in morbidly obese subjects. Anesth Analg 2011;113:57–62.
Bioelectric impedance analysis in body composition measurement. National institutes of health technology assessment conference statement. Am J Clin Nutr. 1996;64(suppl):524S–32S.
Gray DS, Bray GA, Gemayel N, et al. Effect of obesity on bioelectrical impedance. Am J Clin Nutr. 1989;50:255–60.
Zarowitz BJ. Bioelectrical impedance analysis measurements for drug pharmacokinetics. Am J Clin Nutr. 1996;64(suppl):519S–23S.
Thibault R, Genton L, Pichard C. Body composition: why, when and for who? Clin Nutr. 2012;31:435–47.
Coppini LZ, Waitzberg DL, Campos AC. Limitations and validation of bioelectrical impedance analysis in morbidly obese patients. Curr Opin Clin Nutr Metab Care. 2005;8:329–32.
Ismael S, Savalle M, Trivin C, Gillaizeau F, D’Auzac C, Faisy C. The consequences of sudden fluid shifts on body composition in critically ill patients. Crit Care. 2014;18:R49.
Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health-Syst Pharm. 2009;66:642–8.
Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004;58:119–33.
Pai MP, Nafziger AM, Bertino JS. Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother. 2011;55:4006–11.
Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998;54:621–5.
Alexander JK, Dennis EW, Smight WG, et al. Blood volume, cardiac output, and distribution of systemic blood flow in obesity. Cardiovasc Res Centr Bull. 1963;962:39–44.
Manzone TA, Dam HQ, Soltis D, Sagar VV. Blood volume analysis: a new technique and new clinical interest reinvigorate a classic study. J Nucl Med Technol. 2007;35:55–63.
Anastasio P, Spitali L, Frangiosa A, et al. Glomerular filtration in severely overweight normotensive humans. Am J Kidney Dis. 2000;35:1144–8.
Lemoine S, Guebre-Egziabher F, Sens F, et al. Accuracy of GFR estimation in obese patients. Clin J Am Soc Nephrol. 2014;9:720–7.
Brill MJ, Diepstraten J, van Rongen A, et al. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51:277–304.
McLeay SC, Morrish GA, Kirkpatrick CM, Green B. The relationship between drug clearance and body size. Clin Pharmacokinet. 2012;51:319–30.
Knibbe CA, Brill MJ, van Rongen A, Diepstraten J, van der Graaf PH, Danhof M. Drug disposition in obesity: towards evidence-based dosing. Annu Rev Pharmacol Toxicol. 2015;55:149–67.
Gibney MA, Aree CH, Byron KJ, Hirsch LJ. Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations. Curr Med Res Opin. 2010;26:1519–30.
Schwartz S, Hassman D, Shelmet J, et al. A multicenter, open-label, randomized, two-period crossover trial comparing glycemic control, satisfaction, and preference achieved with a 31 gauge × 6 mm needle versus a 29 gauge × 12.7 mm needle in obese patients with diabetes mellitus. Clin Ther. 2004;26:1663–78.
Clauson PG, Linde B. Absorption of rapid-acting insulin in obese and non-obese NIDDM patients. Diab Care. 1995;18:986–91.
Gagnon-Auger M, Du Souich P, Baillargeon JP, et al. Dose-dependent delay of the hypoglycemic effect of short-acting insulin analogs in obese subjects with Type 2 diabetes. Diab Care. 2010;33:2502–7.
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;84:1341–9.
Carvalho B, Collins J, Drover DR, Ralls LA, Riley ET. ED50 and ED95 of intrathecal bupivacaine in morbidly obese patients undergoing Cesarean delivery. Anesthesiology. 2011;114:529–35.
Jain R, Chung SM, Jain L, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther. 2011;90:77–89.
Jacques KA, Erstad BL. Availability of information for dosing injectable medications in underweight or obese patients. Am J Health-Syst Pharm. 2010;67:1948–50.
Harskamp-van Ginkel MW, Hill KD, Becker K, et al. Drug dosing and pharmacokinetics in children with obesity: a systematic review. JAMA Pediatr. 2015;169:678–85.
Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology Practice Guidelines. J Clin Oncol. 2012;30:1553–61.
Bubalo J, Carpenter PA, Majhail N, et al. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation Practice Guideline Committee. Biol Blood Marrow Transplant. 2014;20:600–16.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflicts of interest for the author.
Funding
No funding was obtained.
Rights and permissions
About this article
Cite this article
Erstad, B.L. Improving Medication Dosing in the Obese Patient. Clin Drug Investig 37, 1–6 (2017). https://doi.org/10.1007/s40261-016-0461-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40261-016-0461-4