Specifics of pharmacotherapy in obese patients

Česká verzia

Authors: Alena Pilková ^1,2; Jan Miroslav Hartinger ^1,2
Authors place of work: Oddělení klinické farmakologie a farmacie VFN v Praze ¹; Farmakologický ústav 1. LF UK a VFN v Praze ²
Published in the journal: Forum Diab 2023; 12(1): 19-29
Category:

Summary

Obese patients represent an expanding group of individuals within healthcare, yet precise data on drug dosing adjustments with regard to obesity are not available for majority of drugs. Especially patients with Class III obesity are in clinical often underrepresented in clinical trials. Failure to account for changed body parameters when dosing drugs can lead to insufficient effect or accumulation in adipose tissue. This article presents an overview of body composition descriptors and information about expected changes in pharmacokinetic parameters that may affect the drug body transfer and thus its effect. This overview is followed by examples of several drug groups commonly used in clinical practice.

Keywords:

antidiabetics – Body weight – Anticoagulants – body mass index – volume of distribution – clearance – antiarrythmics – hepatal functions – renal functions

Zdroje

1. WHO. Obesity and Overweight. Dostupné z WWW: <https://www.who.it>. [29–01–2023].

2. Hartinger JM. Novinky ve farmakoterapii obezity. Prakt Lékáren 2021; 17(2): 74–80.

3. Rocca B, Fox KAA, Ajjan RA et al. Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. Eur Heart J 2018; 39(19): 1672–1686f. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehy066>.

4. Pai MP. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacotherapy 2012; 32(9): 856–868. Dostupné z DOI: <http://dx.doi.org/10.1002/j.1875–9114.2012.01108.x>.

5. Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 2010; 49(2): 71–87. Dostupné z DOI: <http://dx.doi.org/10.2165/11318100–000000000–00000>.

6. WHO expert consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004; 363(9403): 157–163. Dostupné z DOI: <http://dx.doi.org/10.1016/s0140–6736(03)15268–3>.

7. May M, Schindler C, Engeli S. Modern pharmacological treatment of obese patients. Ther Adv Endocrinol Metab 2020; 11: 2042018819897527. Dostupné z DOI: <http://dx.doi.org/10.1177/2042018819897527>.

8. Griggs JJ, Mangu PB, Anderson H 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): 1553–1561. Dostupné z DOI: <http://dx.doi.org/10.1200/JCO.2011.39.9436>.

9. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39(3): 215–231. Dostupné z DOI: <http://dx.doi.org/10.2165/00003088–200039030–00004>.

10. Heading RC, Nimmo J, Prescott LF et al. The dependence of paracetamol absorption on the rate of gastric emptying. Br J Pharmacol 1973; 47(2): 415–421. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1476–5381.1973.tb08339.x>.

11. 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: a pharmacokinetic and pharmacodynamic study. Diabetes Care 2010; 33(12): 2502–2507. Dostupné z DOI: <http://dx.doi.org/10.2337/dc10–1126>.

12. 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(12): 167–176. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cjca.2014.10.025>.

13. Strohfus P, Palma S, Wallace CT. Dorsogluteal intramuscular injection depth needed to reach muscle tissue according to body mass index and gender: A systematic review. J Clin Nurs 2022; 31(19–20): 2943–2958. Dostupné z DOI: <http://dx.doi.org/10.1111/jocn.16126>.

14. Cook IF, Williamson M, Pond D. Definition of needle length required for intramuscular deltoid injection in elderly adults: an ultrasonographic study. Vaccine 2006; 24(7): 937–940. DOI: 10.1016/j.vaccine. 2005.08.098

15. Moore KT. Special Populations: Profiling the Effect of Obesity on Drug Disposition and Pharmacodynamics. In: Hock FJ, Gralinski MR (eds). Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer International Publishing: Cham 2019: 1–25. ISBN 978–3319688633. Dostupné z DOI: <http://dx.doi.org/10.1007/978–3-319–56637–5_7–1>.

16. Pilkova A, Hartinger MJ. Změny farmakokinetiky léčiv u obézních pacientů. Vnitř Lék 2020; 66(8): 465–471.

17. Smit C, De Hoogd S, Brüggemann RJM et al. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol 2018; 14(3): 275–285. Dostupné z DOI: <http://dx.doi.org/10.1080/17425255.2018.1440287>.

18. Andrews LM, de Winter BC, Tang JT et al. Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose. Transplant Direct 2017; 3(2): e129. Dostupné z DOI: <http://dx.doi.org/10.1097/txd.0000000000000644>.

19. Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity. Determination of loading dose. Arch Neurol 1985; 42(5): 468–471. Dostupné z DOI: <http://dx.doi.org/10.1001/archneur.1985.04060050066010>.

20. Monografie uvedených přípravků. Databáze Micromedex® (elektronická verze). Merative, Ann Arbor, Michigan, USA. Dostupné z: <https://www.micromedexsolutions.com>. (citováno: 30.1.2023).

21. Hartinger JM, Šíma M, Hronová K et al. Vancomycin pharmacokinetics in patients treated with intermittent haemodialysis based on therapeutic drug monitoring. J Chemother 2022; 34(3): 149–156. Dostupné z DOI: <http://dx.doi.org/10.1080/1120009X.2021.1979747>.

22. Meng L, Mui E, Holubar MK et al. Comprehensive Guidance for Antibiotic Dosing in Obese Adults. Pharmacotherapy. 2017; 37(11): 1415–1431. Dostupné z DOI: <http>//doi: 10.1002/phar.2023>. Erratum in: Pharmacotherap. 2018; 38(2); 302. PMID: 28869666.

23. Platná SPC léčiv obsahujících výše uvedené účinné látky. Dostupné z WWW: <http://www.sukl.cz>.

24. 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(5): 277–304. Dostupné z DOI: <http://dx.doi.org/10.2165/11599410–000000000–00000>.

25. 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): 604–612. Dostupné z DOI: <http://dx.doi.org/10.1002/j.1875–9114.2012.01098.x>.

26. Abernethy DR, Greenblatt DJ, Divoll M et al. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med 1983; 101(6): 873–880.

27. Tellor KB, Nguyen SN, Bultas AC et al. Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients. Ther Adv Cardiovasc Dis 2018; 12(8): 207–216. Dostupné z DOI: <http://dx.doi.org/10.1177/1753944718781295>.

28. Wallace JL, Reaves AB, Tolley EA et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 2013; 36(1): 96–101. Dostupné z DOI: <http://dx.doi.org/10.1007/s11239–012–0811-x>.

29. Reilly PA, Lehr T, Haertter S et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014; 63(4): 321–328. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2013.07.104>.

30. Pracovní skupina pro farmakoterapie obézních pacientů. ČOSKF ČLS JEP. Dostupné z WWW: <https://coskf.cz>. [29–01–2023].

31. Boriani G, Ruff CT, Kuder JF et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation at the Extremes of Body Weight: An Analysis from the ENGAGE AF-TIMI 48 Trial. Thromb Haemost 2021; 121(2): 140–149. Dostupné z DOI: <http://dx.doi.org/10.1055/s-0040–1716540>.

32. Kido K, Lee JC, Hellwig T et al. Use of Direct Oral Anticoagulants in Morbidly Obese Patients. Pharmacotherapy 2020; 40(1): 72–83. Dostupné z DOI: <http://dx.doi.org/10.1002/phar.2353>.

33. Platná SPC léčiv obsahujících výše uvedené účinné látky. Dostupné z WWW: <http://www.sukl.cz>.

34. Garcia DA, Baglin TP, Weitz JI et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e24S-e43S. Dostupné z DOI: <http://dx.doi.org/10.1378/chest.11–2291>.

35. Fraisse F, Holzapfel L, Couland JM et al. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The Association of Non-University Affiliated Intensive Care Specialist Physicians of France. Am J Respir Crit Care Med 2000; 161(4 Pt 1): 1109–1114. Dostupné z DOI: <http://dx.doi.org/10.1164/ajrccm.161.4.9807025>.

36. Borkgren-Okonek MJ, Hart RW, Pantano JE et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008; 4(5): 625–631. Dostupné z DOI: <http://dx.doi.org/10.1016/j.soard.2007.11.010>.

37. Wang TF, Milligan PE, Wong CA et al. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost 2014; 111(1): 88–93. Dostupné z DOI: <http://dx.doi.org/10.1160/th13–01–0042>.

38. Schijns W, Deenen MJ, Aarts EO et al. The Effect of Obesity on Anti-Xa Concentrations in Bariatric Patients. Obes Surg 2018; 28(7): 1997–2005. Dostupné z DOI: <http://dx.doi.org/10.1007/s11695–018–3130–2>.

39. Hirmerová J, Karetová D, Malý R et al. Akutní žilní trombóza 2014: Současný stav prevence, diagnostiky a léčby. Doporučený postup České angiologické společnosti ČLS JEP. Dostupné z WWW: <https://csth.cz>. [29–01–2023].

40. Geerts WH, Bergqvist D, Pineo GF et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(6 Suppl): 381S-453S. Dostupné z DOI: <http://dx.doi.org/10.1378/chest.08–0656>.

41. Kahn SR, Lim W, Dunn AS et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e195S-e226S. Dostupné z DOI: <http://dx.doi.org/10.1378/chest.11–2296>.

42. Fukuchi H, Nakashima M, Araki R et al. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. J Clin Pharm Ther 2009; 34(3): 329–336. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365–2710.2008.00987.x>.

43. Koike H, Fujino T, Koike M et al. Obesity Is Associated With the Development of Interstitial Pneumonia Under Long-Term Administration of Amiodarone in Refractory Atrial Fibrillation Patients. Int Heart J 2016; 57(1): 30–34. Dostupné z DOI: <http://dx.doi.org/10.1536/ihj.15–276>.

44. Abernethy DR, Greenblatt DJ, Smith TW. Digoxin disposition in obesity: clinical pharmacokinetic investigation. Am Heart J 1981; 102(4): 740–744. Dostupné z DOI: <http://dx.doi.org/10.1016/0002–8703(81)90100–9>.

45. Lee LS, Chan LN. Evaluation of a sex-based difference in the pharmacokinetics of digoxin. Pharmacotherapy 2006; 26(1): 44–50. Dostupné z DOI: <http://dx.doi.org/10.1592/phco.2006.26.1.44>.

46. Le Jeunne C, Poirier JM, Cheymol G et al. Pharmacokinetics of intravenous bisoprolol in obese and non-obese volunteers. Eur J Clin Pharmacol 1991; 41(2): 171–174. Dostupné z DOI: <http://dx.doi.org/10.1007/bf00265912>.

47. Galletti F, Fasano ML, Ferrara LA et al. Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects. J Clin Pharmacol 1989; 29(3): 212–216. Dostupné z DOI: <http://dx.doi.org/10.1002/j.1552–4604.1989.tb03315.x>.

48. 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): 961–968. Dostupné z DOI: <http://dx.doi.org/10.1007/s00228–011–1207–0>.

49. Galvus: EPAR – Scientific Discussion. Dostupné z WWW: <https://www.ema.europa.eu>. [08–07–2021].

50. Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab 2010; 12(8): 648–658. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463–1326.2010.01212.x>.