European Journal of Clinical Pharmacology

, Volume 24, Issue 5, pp 643–647 | Cite as

Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients

  • L. A. Bauer
  • W. A. Drew Edwards
  • E. Patchen Dellinger
  • D. A. Simonowitz


Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (>90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). The results were similar for all 3 drugs. Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.31 and 135.8 ml/min for gentamicin, 29.01 and 162.4 ml/min for tobramycin, and 26.81 and 157.3 ml/min for amikacin) than in normal weight patients (17.01 and 95.9 ml/min for gentamicin, 18.31 and 101.3 ml/min for tobramycin, and 18.61 and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p<0.005) in order to achieve comparable serum concentrations.

Key words

aminoglycosides obesity altered pharmacokinetics gentamicin tobramycin amikacin gram-negative infection 


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  1. 1.
    Abernethy DR, Divoll M, Greenblatt DJ, Ameer B (1982) Obesity, sex and acetaminophen disposition. Clin Pharmacol Ther 31: 783–790Google Scholar
  2. 2.
    Abernethy DR, Greenblatt DJ, Divoll M, Harmaty JS, Shader RI (1981) Alterations in drug disposition and clearance due to obesity. J Pharmacol Exp Ther 217: 681–685Google Scholar
  3. 3.
    Abernethy DR, Greenblatt DJ, Smith TW (1981) Digoxin disposition in obesity — clinical pharmacokinetic investigation. Am Heart J 102: 740–744Google Scholar
  4. 4.
    Barza M, Brown RB, Shen D, Gibaldi M, Weinstein L (1975) Predictability of blood levels of gentamicin in man. J Infect Dis 132: 165–174Google Scholar
  5. 5.
    Bauer LA, Blouin RA, Griffen WO, Record KE, Bell RM (1980) Amikacin pharmacokinetics in morbidly obese patients. Am J Hosp Pharm 37: 519–522Google Scholar
  6. 6.
    Blouin RA, Bauer LA, Miller DD, Record KE, Griffen WO (1982) Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 21: 575–580Google Scholar
  7. 7.
    Blouin RA, Elgert JF, Bauer LA (1980) Theophylline clearance — effect of marked obesity. Clin Pharmacol Ther 28: 619–623Google Scholar
  8. 8.
    Blouin RA, Mann HJ, Griffen WO, Bauer LA, Record KE (1979) Tobramycin pharmacokinetics in morbidly obese patients. Clin Pharmacol Ther 26: 508–512Google Scholar
  9. 9.
    Devine BJ (1974) Gentamicin therapy. Drug Intell Clin Pharm 8: 650–655Google Scholar
  10. 10.
    Dionne RE, Bauer LA, Gibson GA, Griffen WO, Blouin RA (1981) Estimating creatinine clearance in morbidly obese patients. Am J Hosp Pharm 38: 841–844Google Scholar
  11. 11.
    Ewy GA, Graves BM, Ball MF, Nimmo L, Jackson B, Marcus F (1971) Digoxin metabolism in obesity. Circulation 44: 810–815Google Scholar
  12. 12.
    Gal P, Jusko WJ, Yurchak AM, Franklin BA (1978) Theophylline disposition in obesity. Clin Pharmacol Ther 23: 438–444Google Scholar
  13. 13.
    Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New YorkGoogle Scholar
  14. 14.
    Koeppe P, Hamann C (1980) A program for nonlinear regression analysis to be used on desk-top computers. Comput Prog Biomed 12: 121–128Google Scholar
  15. 15.
    Korsager S (1980) Administration of gentamicin to obese patients. Int J Clin Pharmacol Ther Toxicol 18: 549–553Google Scholar
  16. 16.
    Morse WI, Soeldner JS (1963) The composition of adipose tissue and the nonadipose body of obese and nonobese man. Metabolism 12: 99–107Google Scholar
  17. 17.
    Sarubbi FA, Hull JH (1978) Amikacin serum concentrations — prediction of levels and dosage guidelines. Ann Intern Med 89: 612–618Google Scholar
  18. 18.
    Schwartz SN, Pazin GJ, Lyon JA, Ho M Pasculle AW (1978) A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis 138: 499–505Google Scholar
  19. 19.
    Siber GR, Echeverria P, Smith AL, Paisley JW, Smith DH (1975) Pharmacokinetics of gentamicin in children and adults. J Infect Dis 132: 637–651Google Scholar
  20. 20.
    Sketris I, Lesar T, Zaske DE, Cipolle RJ (1981) Effect of obesity on gentamicin pharmacokinetics. J Clin Pharmacol 21: 289–293Google Scholar
  21. 21.
    Stokholm KH, Brochner-Mortensen J, Hoilund-Carlsen PF (1980) Increased glomerular filtration rate and adrenocortical function in obese women. Int J Obesity 4: 57–63Google Scholar
  22. 22.
    DuBois D, DuBois EF (1915) The measurement of the surface area of man. Arch Intern Med 15: 868–881Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • L. A. Bauer
    • 1
    • 2
  • W. A. Drew Edwards
    • 1
  • E. Patchen Dellinger
    • 2
  • D. A. Simonowitz
    • 2
  1. 1.School of PharmacyUniversity of WashingtonSeattleUSA
  2. 2.School of MedicineUniversity of WashingtonSeattleUSA

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