Authors: Alena Pilková Authors‘ workplace: Farmakologický ústav 1. LF UK a VFN v Praze Published in: Čes. slov. Farm., 2026; 75, 16-22 Category: Review Article doi: https://doi.org/10.36290/csf.2026.004
Introduction: Obesity is a chronic disease associated with multiple comorbidities and can affect drug pharmacokinetics. Appropriate dosing in obese patients is essential to ensure therapeutic efficacy and safety.
Objective: To summarize the impact of obesity and bariatric surgery on drug pharmacokinetics and provide recommendations for individualized dosing.
Methods: Review of available literature and clinical guidelines addressing changes in drug absorption, distribution, metabolism, and excretion in obese patients and after bariatric procedures.
Results: Obesity is associated with nonlinear changes in volume of distribution and heterogenous changes in clearance: modification of certain CYP enzyme activity (notably CYP3A4, CYP2C19, CYP2E1), and alteration of renal function. Anatomical and functional chages of gastrointestinal tract (GIT) following bariatric surgery variably modify absorption area, pH, GIT motility and lead to improvement in metabolic comorbidities. Dose adjustments are particularly important for drugs with a narrow therapeutic range, weight-based dosing regimens, and highly lipophilic substances. An individualized approach and therapeutic drug monitoring are recommended in clinical practice.
Conclusion: Universal drug dosing regimens for obese patients or those after bariatric surgery are unavailable for most drugs. Body composition and other patient-specific factors, as well as drug pharmacokinetics should be considered. Clinical pharmacists can contribute to optimal pharmacotherapy in this heterogeneous population.
obesity – Therapeutic drug monitoring – pharmacokinetics – bariatric surgery – drug dosing
1. Busetto L, Dicker D, Frühbeck G, et al. A new framework for the diagnosis, staging and management of obesity in adults. Nat Med. 2024;30(9):2395-9.
2. Pai MP. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacotherapy. 2012;32(9):856-68.
3. Ohlendorf D, Avaniadi I, Adjami F, et al. Standard values of the upper body posture in healthy adults with special regard to age, sex and BMI. Sci Rep. 2023;13(1):873.
4. Greenblatt DJ. The Seventy-Kilogram Fantasy. Clin Pharmacol Drug Dev. 2013;2(2):101-2.
5. Overweight and obesity. Available from: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Overweight_and_obesity_-_BMI_statistics; cit. 12. 12. 2025.
6. Sweatt K, Garvey WT, Martins C. Strengths and Limitations of BMI in the Diagnosis of Obesity: What is the Path Forward? Curr Obes Rep. 2024;13(3):584-95.
7. Pilkova A. Doporucene davkovani antikoagulancii v dobe pandemie obezity. Vnitrni lekarstvi. 2024;70(1):60-5.
8. Zheng H. It Is Time to Abandon the Use of Body Surface Area Derived From a 100-Year-Old Formula. Am J Med. 2022;135(9):e308-e10.
9. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate Systemic Therapy Dosing for Obese Adult Patients With Cancer: ASCO Guideline Update. J Clin Oncol. 2021;39(18):2037-48.
10. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4s):S117-s314.
11. Gouju J, Legeay S. Pharmacokinetics of obese adults: Not only an increase in weight. Biomed Pharmacother. 2023;166 : 115281.
12. Pilková A HJ. Změny farmakokinetiky u obézních pacientů. Via Pract. 2024(21(1)):6-10.
13. Stillhart C, Vučićević K, Augustijns P, Basit AW, Batchelor H, Flanagan TR, et al. Impact of gastrointestinal physiology on drug absorption in special populations--An UNGAP review. Eur J Pharm Sci. 2020;147 : 105280.
14. Foegh M, Archer DF, Stanczyk FZ, et al. Ovarian activity in obese and nonobese women treated with three transdermal contraceptive patches delivering three different doses of ethinyl estradiol and levonorgestrel. Contraception. 2013;87(2):201-11.
15. Databáze léků SÚKL. Státní ústav pro kontrolu léčiv. Dostupné z www.sukl.cz. Stav k 12. 12. 2025
16. Vaccine Administration: Needle Gauge and Length. Available from: https://www.
cdc.gov/vaccines/hcp/admin/downloads/vaccine-administration-needle-length.pdf; cit. 12. 12. 2025.
17. Erstad BL, Barletta JF. Implications of obesity for drug administration and absorption from subcutaneous and intramuscular injections: A primer. Am J Health Syst Pharm. 2022;79(15):1236-44.
18. Gaudio FG, Johnson DE, DiLorenzo K, Anderson A, Musi M, Schimelpfenig T, et al. Wilderness Medical Society Clinical Practice Guidelines on Anaphylaxis. Wilderness Environ Med. 2022;33(1):75-91.
19. Berton M, Bettonte S, Stader F, Battegay M, Marzolini C. Physiologically Based Pharmacokinetic Modelling to Identify Physiological and Drug Parameters Driving Pharmacokinetics in Obese Individuals. Clin Pharmacokinet. 2023;62(2):277-95.
20. Pilkova A, Hartinger MJ. Zmeny farmakokinetiky leciv u obeznich pacientu. Vnitrni lekarstvi. 2020;66(8):465-71.
21. Kvitne KE, Hjelmesæth J, Hovd M, et al. Oral Drug Dosing After Gastric Bypass and Diet-Induced Weight Loss: Simpler Than We Think? Lessons Learned From the COCKTAIL Study. Clin Pharmacol Ther. 2024;116(3):647-52.
22. Rodríguez-Morató J, Goday A, Langohr K, et al. Short - and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity. Sci Rep. 2019;9(1):20405.
23. Aubert J, Begriche K, Knockaert L, et al. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol. 2011;35(10):630-7.
24. García-Carro C, Vergara A, Bermejo S, et al. A Nephrologist Perspective on Obesity: From Kidney Injury to Clinical Management. Front Med (Lausanne). 2021;8 : 655871.
25. Pilková A, Hartinger JM. Změny farmakokinetiky pacientů s obezitou. In Fábryová L. Klinická obezitológia, 2nd ed., 202-212. Brno: Facta Medica; 2023.
26. European Medicines Agency. Reflection paper on investigation of pharmacokinetics and pharmacodynamics in the obese population. Dostupné z https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-investigation-pharmacokinetics-obese-population-scientific-guideline_en.pdf; přístup 12.12.2025.
27. Meng L, Mui E, Ha DR, et al. Comprehensive guidance for antibiotic dosing in obese adults: 2022 update. Pharmacotherapy. 2023;43(3):226-46.
28. Strojil J. Aktualni doporuceni pro davkovani antibiotik u obeznich pacientu. Vnitrni lekarstvi. 2024;70(5):295-302.
29. Gigante B, Tamargo J, Agewall S, et al. Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis. Eur Heart J Cardiovasc Pharmacother. 2024;10(7):614-45.
30. Martin KA, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021;19(8):1874-82.
31. Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth. 2010;105 Suppl 1:i16-23.
32. Lin L, van der Meer EKO, Steeghs N, et al. Are novel oral oncolytics underdosed in obese patients? Cancer Chemother Pharmacol. 2024;93(2):129-36.
33. 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.
34. Mueller JA, Patel T, Halawa A, et al. Warfarin dosing and body mass index. Ann Pharmacother. 2014;48(5):584-8.
35. White PJ. Patient factors that influence warfarin dose response. J Pharm Pract. 2010;23(3):194-204.
36. Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis. Crit Care. 2021;25(1):77.
37. Bruno CD, Greenblatt DJ, Harmatz JS, Chow CR. Clinical Consequences of Altered Drug Disposition in Obesity: Call for Change. J Clin Pharmacol. 2023;63 Suppl 2:S25-s34.
38. Moiz A, Filion KB, Tsoukas MA, et al. The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions. EClinicalMedicine. 2025;86 : 103363.
39. Haluzik M, Jakubikova I, Kudlackova M, Horvath L. Aktualni moznosti lecby obezity. Medicine for Practice. 2023;20(4):230-4.
40. Min JS, Jo SJ, Lee S, et al. A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist. Drug Des Devel Ther. 2025;19 : 3509-37.
41. Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Endocr Pract. 2013;19(2):337-72.
42. Kingma JS, Burgers DMT, Monpellier VM, Wiezer MJ, Blussé van Oud-Alblas HJ, Vaughns JD, et al. Oral drug dosing following bariatric surgery: General concepts and specific dosing advice. Br J Clin Pharmacol. 2021;87(12):4560-76.
43. Ladebo L, Pedersen PV, Pacyk GJ, et al. Gastrointestinal pH, Motility Patterns, and Transit Times After Roux-en-Y Gastric Bypass. Obes Surg. 2021;31(6):2632-40.
44. Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, Zeldin DC. The human intestinal cytochrome P450 "pie". Drug Metab Dispos. 2006;34(5):880-6.
45. Dvořáčková E, Pilková A, Matoulek M, et al. Bioavailability of Orally Administered Drugs After Bariatric Surgery. Curr Obes Rep. 2024.
46. Adams TD, Davidson LE, Litwin SE, et al. Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med. 2017;377(12):1143-55.
47. Pham A, Chan P, Mercado A, et al. Impact of bariatric surgery on cytochrome P 450 enzyme activity. Front Pharmacol. 2024;15 : 1372950.
48. Kvitne KE, Robertsen I, Skovlund E, et al. Short - and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial. Clin Transl Sci. 2022;15(1):221-33.
49. Kvitne KE, Krogstad V, Wegler C, et al. Short - and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity. Br J Clin Pharmacol. 2022;88(9):4121-33.
50. Kvitne KE, Hovd M, Johnson LK, et al. Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals. Clin Pharmacokinet. 2024;63(1):109-20.
51. Hovd M, Robertsen I, Johnson LK, et al. Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance. Clinical Pharmacokinetics. 2023;62(5):725-35.
52. Pilková A, Hartinger J, Slanař O, Matoulek M. Pharmacotherapy of carbamazepine-treated patient after bariatric surgery: a complex interplay between altered absorption and drug-drug interactions. Eur J Hosp Pharm. 2024.
53. Huang H, Lu J, Dai X, et al. Improvement of Renal Function After Bariatric Surgery: a Systematic Review and Meta-analysis. Obes Surg. 2021;31(10):4470-84.
54. Wahlström A, Aydin Ö, Olsson LM, et al. Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes. EBioMedicine. 2024;106 : 105265.
55. Greenblatt HK, Greenblatt DJ. Altered drug disposition following bariatric surgery: a research challenge. Clin Pharmacokinet. 2015;54(6):573-9.
56. Krieger CA, Cunningham JL, Reid JM, et al. Comparison of Bioavailability of Single-Dose Extended-Release Venlafaxine Capsules in Obese Patients Before and After Gastric Bypass Surgery. Pharmacotherapy. 2017;37(11):1374-82.
57. Wallerstedt SM, Nylén K, Axelsson MAB. Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure. Eur J Clin Pharmacol. 2021;77(12):1875-85.
58. Courcoulas AP, Daigle CR, Arterburn DE. Long term outcomes of metabolic/bariatric surgery in adults. Bmj. 2023;383:e071027.
59. Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and Risks of Bariatric Surgery in Adults: A Review. JAMA. 2020;324(9):879-87.
60. Burjonrappa S, Grover K. Bariatric Surgery Complications. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC.; 2025.
61. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247.
62. Abernethy DR, Divoll M, Greenblatt DJ, Ameer B. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther. 1982;31(6):783-90.
63. 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.
64. Goldwater R, Kramer WG, Hamilton DA, et al. A Phase I study evaluating the effect of age and weight on the pharmacokinetics of an injectable formulation of diclofenac solubilized with hydroxypropyl-β-cyclodextrin. Clin Pharmacol. 2016;8 : 203-12.
65. Abernethy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum. 1985;28(10):1117-21.
66. de Hoogd S, Välitalo PAJ, Dahan A, et al. Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide. Clin Pharmacokinet. 2017;56(12):1577-87.
67. Shibutani K, Inchiosa MA, Jr., Sawada K, Bairamian M. Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obese surgical patients: derivation of dosing weight ("pharmacokinetic mass"). Anesthesiology. 2004;101(3):603-13.
68. Kuip EJM, Oldenmenger WH, Thijs-Visser MF, et al. Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer. PLoS One. 2018;13(6):e0198289.
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