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Dosage adjustment in obese children, even for common drugs, is largely unclear and a treat-to-effect approach may work best

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Abstract

Obesity in children, often accompanied by comorbidities, is increasingly common. For many frequently used paediatric drugs, information on dosage adjustment in obese children is lacking or absent. Scalars, such as total body weight, are not always helpful as obese children may weigh more than adults, but differ with regard to aspects of their anatomy and physiology, especially hepatic function. Further pharmacokinetic studies in obese children are urgently needed and, in the interim, close monitoring for therapeutic effect and toxicity is recommended.

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References

  1. Commission on Ending Childhood Obesity (ECHO). Report of the commission on ending childhood obesity. Geneva: World Health Organzation; 2016.

  2. American Academy of Pediatrics. Council on child and adolescent health: age limit of pediatrics. Pediatrics. 1988;81(5):736.

    Google Scholar 

  3. Harskamp-van Ginkel MW, Hill KD, Becker KC, et al. Drug dosing and pharmacokinetics in children with obesity: a systematic review. JAMA Pediatr. 2015;169(7):678–85.

    PubMed  PubMed Central  Google Scholar 

  4. Callaghan LC. Prescribing in paediatric obesity: methods to improve dosing safety in weight-based dose calculations. Arch Dis Child Educ Pract. 2018;103(5):274–7.

    Google Scholar 

  5. Anderson BJ, Holford NH. What is the best size predictor for dose in the obese child? Paediatr Anaesth. 2017;27(12):1176–84.

    PubMed  Google Scholar 

  6. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology: drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.

    CAS  PubMed  Google Scholar 

  7. Kendrick JG, Carr RR, Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing. Clin Ther. 2015;37(9):1897–923.

    CAS  PubMed  Google Scholar 

  8. Kyler KE, Wagner J, Hosey-Cojocari C, et al. Drug dose selection in pediatric obesity: available information for the most commonly prescribed drugs to children. Pediatric Drugs. 2019;21(5):357–69.

    PubMed  Google Scholar 

  9. He Q, Karlberg J. BMI in childhood and its association with height gain, timing of puberty, and final height. Pediatr Res. 2001;49(2):244–51.

    CAS  PubMed  Google Scholar 

  10. McGarry ME, Castellanos E, Thakur N, et al. Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest. 2015;147(6):1591–8.

    PubMed  PubMed Central  Google Scholar 

  11. Knibbe CAJ, Brill MJE, van Rongen A, et al. Drug disposition in obesity: toward evidence-based dosing. Annu Rev Pharmacol Toxicol. 2015;55:149–67.

    CAS  PubMed  Google Scholar 

  12. Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71–877.

    CAS  PubMed  Google Scholar 

  13. Benedek IH, Blouin RA, McNamara PJ. Serum protein binding and the role of increased alpha 1-acid glycoprotein in moderately obese male subjects. Br J Clin Pharmacol. 1984;18(6):941–6.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–233.

    PubMed  PubMed Central  Google Scholar 

  16. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998;54(8):621–5.

    CAS  PubMed  Google Scholar 

  17. Rowe S, Siegel D, Benjamin DK. Gaps in drug dosing for obese children: a systematic review of commonly prescribed emergency care medications. Clin Ther. 2015;37(9):1923–32.

    Google Scholar 

  18. Small BG, Wendt B, Jamei M, et al. Prediction of liver volume: a population-based approach to meta-analysis of paediatric, adult and geriatric populations—an update. Biopharm Drug Dispos. 2017;38(4):290–300.

    CAS  PubMed  Google Scholar 

  19. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39(3):215–31.

    CAS  PubMed  Google Scholar 

  20. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346(16):1221–31.

    CAS  PubMed  Google Scholar 

  21. Pediatric Trials Network (PTN). Available frome https://pediatrictrials.org/. Accessed 31 Mar 2020.

  22. Zheng Y, Liu SP, Xu BP. Population pharmacokinetics and dosing optimization of azithromycin in children with community-acquired pneumonia. Antimicrob Agents Chemother. 2018;62:e00686–718.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Natale S, Bradley J, Nguyen WH, et al. Pediatric obesity: pharmacokinetic alterations and effects on antimicrobial dosing. Pharmacotherapy. 2017;37(3):361–78.

    CAS  PubMed  Google Scholar 

  24. Koshida R, Nakashima E, Taniguchi N, et al. Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts. Pharm Res. 1989;6(6):486–91.

    CAS  PubMed  Google Scholar 

  25. Schmitz ML, Blumer JL, Cetnarowski W, et al. Determination of appropriate weight-based cutoffs for empiric cefazolin dosing using data from a phase 1 pharmacokinetics and safety study of cefazolin administered for surgical prophylaxis in pediatric patients aged 10 to 12 years. Antimicrob Agents Chemother. 2015;59(7):4173–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Smith MJ, Gonzalez D, Goldman JL, et al. Pharmacokinetics of clindamycin in obese and nonobese children. Antimicrob Agents Chemother. 2017;61(4):e02014–e2016.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Madigan T, Sieve RM, Graner KK, et al. The effect of age and weight on vancomycin serum trough concentrations in pediatric patients. Pharmacotherapy. 2013;33(12):1264–72.

    CAS  PubMed  Google Scholar 

  28. Nassar L, Hadad S, Gefen A, et al. Prospective evaluation of the dosing regimen of vancomycin in children of different weight categories. Curr Drug Saf. 2012;7(5):375–81.

    CAS  PubMed  Google Scholar 

  29. Le J, Capparelli EV, Wahid U. Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case–control study. Clin Ther. 2015;37(6):1340–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Eiland LS, Sonawane KB. Vancomycin dosing in healthy-weight, overweight, and obese pediatric patients. J Pediatr Pharmacol Ther. 2014;19(3):182–8.

    PubMed  PubMed Central  Google Scholar 

  31. Moffett BS, Kim S, Edwards MS. Vancomycin dosing in obese pediatric patients. Clin Pediatr (Phila). 2011;50(5):442–6.

    Google Scholar 

  32. Heble DE, McPherson C, Nelson MP, et al. Vancomycin trough concentrations in overweight or obese pediatric patients. Pharmacotherapy. 2013;33(12):1273–7.

    CAS  PubMed  Google Scholar 

  33. Barshop NJ, Capparelli EV, Sirlin CB, et al. Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2011;52(2):198–202.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Goday Arno A, Farré M, Rodríguez-Morató J, et al. Pharmacokinetics in morbid obesity: influence of two bariatric surgery techniques on paracetamol and caffeine metabolism. Obes Surg. 2017;27(12):3194–201.

    PubMed  Google Scholar 

  35. van Rongen A, Välitalo PAJ, Peeters MYM, et al. Morbidly obese patients exhibit increased CYP2E1-mediated oxidation of acetaminophen. Clin Pharmacokinet. 2016;55(7):833–47.

    PubMed  PubMed Central  Google Scholar 

  36. Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther. 1982;31(6):783–90.

    CAS  PubMed  Google Scholar 

  37. Vaughns JD, Ziesenitz VC, Williams EF, et al. Use of fentanyl in adolescents with clinically severe obesity undergoing bariatric surgery: a pilot study. Paediatr Drugs. 2017;19(3):251–7.

    PubMed  PubMed Central  Google Scholar 

  38. Samuels PJ, Sjoblom MD. Anesthetic considerations for pediatric obesity and adolescent bariatric surgery. Curr Opin Anaesthesiol. 2016;29(3):327–36.

    CAS  PubMed  Google Scholar 

  39. Shibutani K, Inchiosa MA, Sawada K, et al. Pharmacokinetic mass of fentanyl for postoperative analgesia in lean and obese patients. Br J Anaesth. 2005;95(3):377–83.

    CAS  PubMed  Google Scholar 

  40. Vaughns JD, Ziesenitz VC, van den Anker JN. Clinical pharmacology of frequently used intravenous drugs during bariatric surgery in adolescents. Curr Pharm Des. 2015;21(39):5650–9.

    CAS  PubMed  Google Scholar 

  41. Diepstraten J, Chidambaran V, Sadhasivam S, et al. An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children. CPT Pharmacometrics Syst Pharmacol. 2013;2(8):543–51.

    Google Scholar 

  42. Olutoye OA, Yu X, Govindan K, et al. The effect of obesity on the ED95 of propofol for loss of consciousness in children and adolescents. Anesth Analg. 2012;115(1):147–53.

    CAS  PubMed  Google Scholar 

  43. Meyhoff CS, Lund J, Jenstrup MT, et al. Should dosing of rocuronium in obese patients be based on ideal or corrected body weight? Anesth Analg. 2009;109(3):787–92.

    CAS  PubMed  Google Scholar 

  44. Leykin Y, Pellis T, Lucca M, et al. 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.

    PubMed  Google Scholar 

  45. van Rongen A, Brill MJE, Vaughns JD, et al. Higher midazolam clearance in obese adolescents compared with morbidly obese adults. Clin Pharmacokinet. 2018;57(5):601–11.

    PubMed  Google Scholar 

  46. van Rongen A, Vaughns JD, Moorthy GS, et al. Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents. Br J Clin Pharmacol. 2015;80(5):1185–96.

    PubMed  PubMed Central  Google Scholar 

  47. Goleva E, Covar R, Martin RJ, et al. Corticosteroid pharmacokinetic abnormalities in overweight and obese corticosteroid resistant asthmatics. J Allergy Clin Immunol Pract. 2016;4(2):357.e2–60.e2.

    Google Scholar 

  48. Pelaia G, Vatrella A, Busceti MT, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators Inflamm. 2015;2015:879873.

    Google Scholar 

  49. Anderson WJ, Lipworth BJ. Does body mass index influence responsiveness to inhaled corticosteroids in persistent asthma? Ann Allergy Asthma Immunol. 2012;108(4):237–42.

    CAS  PubMed  Google Scholar 

  50. Farzan S, Khan S, Elera C, et al. Effectiveness of montelukast in overweight and obese atopic asthmatics. Ann Allergy Asthma Immunol. 2017;119(2):189–90.

    CAS  PubMed  Google Scholar 

  51. van Rongen A, van der Aa MP, Matic M, et al. Increased metformin clearance in overweight and obese adolescents: a pharmacokinetic substudy of a randomized controlled trial. Paediatr Drugs. 2018;20(4):365–74.

    PubMed  PubMed Central  Google Scholar 

  52. Bardin C, Nobecourt E, Larger E, et al. Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus. Eur J Clin Pharmacol. 2012;68(6):961–8.

    CAS  PubMed  Google Scholar 

  53. Hanafy S, Pinsk M, Jamali F. Effect of obesity on response to cardiovascular drugs in pediatric patients with renal disease. Pediatr Nephrol. 2009;24(4):815–21.

    PubMed  Google Scholar 

  54. Sankaralingam S, Kim RB, Padwal RS. The impact of obesity on the pharmacology of medications used for cardiovascular risk factor control. Can J Cardiol. 2015;31(2):167–76.

    PubMed  Google Scholar 

  55. Wagner JB, Abdel-Rahman S, Haandel L, et al. Impact of SLCO1B1 genotype on pediatric simvastatin acid pharmacokinetics. J Clin Pharmacol. 2018;58(6):823–33.

    CAS  PubMed  Google Scholar 

  56. Wagner JB, Abdel-Rahman S, Gaedigk R, et al. Impact of genetic variation on pravastatin systemic exposure in pediatric hypercholesterolemia. Clin Pharmacol Ther. 2018;105(6):1501–12.

    Google Scholar 

  57. Stark CM, Nylund CM. Side effects and complications of proton pump inhibitors: a pediatric perspective. J Pediatr. 2016;168:16–22.

    PubMed  Google Scholar 

  58. Shakhnovich V, Abdel-Rahman S, Friesen CA, et al. Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity. Pediatr Obes. 2019;14(1):e12459.

    Google Scholar 

  59. Shakhnovich V, Smith PB, Guptill JT, et al. Obese children require lower doses of pantoprazole than nonobese peers to achieve equal systemic drug exposures. J Pediatr. 2018;193:102–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Shakhnovich V, Smith PB, Guptill JT, et al. A population-based pharmacokinetic model approach to pantoprazole dosing for obese children and adolescents. Paediatr Drugs. 2018;20(5):4853–95.

    Google Scholar 

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The article was written by employees of Adis International Ltd./Springer Nature and was adapted, in part, from Pediatric Drugs 2019;21(5):357–69 [8].

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Writers, A.M. Dosage adjustment in obese children, even for common drugs, is largely unclear and a treat-to-effect approach may work best. Drugs Ther Perspect 36, 341–346 (2020). https://doi.org/10.1007/s40267-020-00734-w

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