International Journal of Clinical Pharmacy

, Volume 33, Issue 6, pp 918–924 | Cite as

Drug dosing and monitoring in obese patients undergoing allogenic stem cell transplantation

  • Claudia LangebrakeEmail author
  • Friederike Bernhardt
  • Michael Baehr
  • Nicolaus Kröger
  • Axel R. Zander
Review Article


Background The effects of physiological changes in patients with obesity on pharmacokinetic parameters and the time course of drug response, especially in the field of haematology/oncology, are poorly understood. For some antimicrobial drugs, dosing considerations exist, while for cytostatic drugs, dose modifications for obese patients are not consistently recommended. Glomerular filtration rate and renal perfusion appear to be similar in obese and normal weight individuals, thus elimination of hydrophilic and extensively renally cleared drugs mainly depends upon creatinine clearance. Aim of the review To provide information about drug dosing in morbidly obese patients undergoing allogenic haematopoietic stem cell transplantation and to develop dosing recommendations for those patients, based on literature data, pharmacokinetic properties and own experiences. Method A review on the literature on drug dosing in obese patients as well as on the pharmacokinetic properties of drugs which are supposed to be used in the field of stem cell transplantation was combined with own data on drug dosing and pharmacokinetic drug monitoring in a morbidly obese patient undergoing matched-unrelated allogenic peripheral blood stem cell transplantation. Results For hydrophilic and extensively renally cleared drugs (e.g. piperacillin/sulbactam, cotrimoxazole, fludarabine) standard dosages for adult patients or dosing based on ideal body weight (IBW) (e.g. aciclovir, methotrexate) can be used. For ciclosporin and digitoxin we could show that high initial doses are needed to achieve sufficient plasma concentrations. After steady state distribution was completed, maintenance doses comparable to normal weight patients are sufficient. Likewise, distribution of enoxaparin and phenytoin seems to take longer in obese patients. Dosing recommendations of 25 drugs that can be used in morbidly obese patients undergoing allogenic stem cell transplantation are given. Conclusions Pharmacotherapy in morbidly obese patients undergoing allogenic stem cell transplantation is possible, if pharmacokinetic properties of the drugs are considered and close monitoring of plasma concentrations is performed.


Drug dosing Obesity Pharmacokinetics Stem cell transplantation 



We thank Dr. Hilke Andresen for the quantification of busulfan plasma concentrations.


No external funding.

Conflicts of interest

There are no conflicts of interest to declare.


  1. 1.
  2. 2.
    Falagas ME, Karageorgopoulos DE. Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet. 2010;375(9710):248–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet. 2000;38(5):415–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007;27(8):1081–91.PubMedCrossRefGoogle Scholar
  5. 5.
    Baker SD, Grochow LB, Donehower RC. Should anticancer drug doses be adjusted in the obese patient? J Natl Cancer Inst. 1995;87(5):333–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Dickson TM, Kusnierz-Glaz CR, Blume KG, et al. Impact of admission body weight and chemotherapy dose adjustment on the outcome of autologous bone marrow transplantation. Biol Blood Marrow Transplant. 1999;5(5):299–305.PubMedCrossRefGoogle Scholar
  7. 7.
    Powis G, Reece P, Ahmann DL, Ingle JN. Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients. Cancer Chemother Pharmacol. 1987;20(3):219–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Georgiadis MS, Steinberg SM, Hankins LA, Ihde DC, Johnson BE. Obesity and therapy-related toxicity in patients treated for small-cell lung cancer. J Natl Cancer Inst. 1995;87(5):361–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71–87.PubMedCrossRefGoogle Scholar
  10. 10.
    Saracino A, Morrone LF, Suriano V, et al. A simple method for correcting overestimated glomerular filtration rate in obese subjects evaluated by the Cockcroft and Gault formula: a comparison with 51Cr EDTA clearance. Clin Nephrol. 2004;62(2):97–103.PubMedGoogle Scholar
  11. 11.
    Pai MP, Norenberg JP, Anderson T, et al. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007;51(8):2741–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Meloni G, Proia A, Capria S, et al. Obesity and autologous stem cell transplantation in acute myeloid leukemia. Bone Marrow Transplant. 2001;28(4):365–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Nguyen L, Leger F, Lennon S, Puozzo C. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol. 2006;57(2):191–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Hollenstein UM, Brunner M, Schmid R, Muller M. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int J Obes Relat Metab Disord. 2001;25(3):354–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Caldwell JB, Nilsen AK. Intravenous ciprofloxacin dosing in a morbidly obese patient. Ann Pharmacother. 1994;28(6):806.PubMedGoogle Scholar
  16. 16.
    Hernandez JO, Norstrom J, Wysock G. Acyclovir-induced renal failure in an obese patient. Am J Health Syst Pharm. 2009;66(14):1288–91.PubMedCrossRefGoogle Scholar
  17. 17.
    Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998;54(8):621–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Flechner SM, Kolbeinsson ME, Tam J, Lum B. The impact of body weight on cyclosporine pharmacokinetics in renal transplant recipients. Transplantation. 1989;47(5):806–10.PubMedCrossRefGoogle Scholar
  19. 19.
    Orofino L, Pascual J, Quereda C, Burgos J, Marcen R, Ortuno J. Influence of overweight on survival of kidney transplant. Nephrol Dial Transplant. 1997;12(4):855.PubMedCrossRefGoogle Scholar
  20. 20.
    Kasap B, Soylu A, Turkmen M, Kavukcu S, Bora S, Gulay H. Effect of obesity and overweight on cyclosporine blood levels and renal functions in renal adolescent recipients. Transplant Proc. 2006;38(2):463–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Yee GC, Lennon TP, Gmur DJ, Cheney CL, Oeser D, Deeg HJ. Effect of obesity on cyclosporine disposition. Transplantation. 1988;45(3):649–51.PubMedCrossRefGoogle Scholar
  22. 22.
    Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity. Determination of loading dose. Arch Neurol. 1985;42(5):468–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6 Suppl):141S–59S.PubMedCrossRefGoogle Scholar
  24. 24.
    Bazinet A, Almanric K, Brunet C, et al. Dosage of enoxaparin among obese and renal impairment patients. Thromb Res. 2005;116(1):41–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Sanderink GJ, Le Liboux A, Jariwala N, et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther. 2002;72(3):308–18.PubMedCrossRefGoogle Scholar
  26. 26.
    Spinler SA, Ou FS, Roe MT, et al. Weight-based dosing of enoxaparin in obese patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE initiative. Pharmacotherapy. 2009;29(6):631–8.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Claudia Langebrake
    • 1
    • 2
    Email author
  • Friederike Bernhardt
    • 1
  • Michael Baehr
    • 2
  • Nicolaus Kröger
    • 1
  • Axel R. Zander
    • 1
  1. 1.Clinic for Stem Cell TransplantationUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.PharmacyUniversity Medical Center Hamburg-EppendorfHamburgGermany

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