The problem of low peak concentration of gentamicin in clinical practice

M. Göböová, M. Kuželová 2 ,  and T. Foltánová 2
  • 1 Department of Clinical Pharmacology, Teaching hospital Nitra
  • 2 Faculty of Pharmacy, Department of Pharmacology and Toxicology, Comenius University in Bratislava

The problem of low peak concentration of gentamicin in clinical practice

Aminoglycoside antibiotics have particular importance in the treatment of Gram-negative infections. Toxicity of gentamicin is well-known, but patients often receive insufficient dosage in clinical practice. The purpose of this study was to refer to the problem of insufficient dosages that were confirmed by low peak concentration and to determine relationship between low peak levels and pharmacokinetic parameters, renal function and body weight.

We studied 68 patients who were treated with gentamicin for one year (August 2010 - August 2011). Therapeutic drug monitoring (TDM) was applied for all the patients. Gentamicin peak and trough concentrations were measured by the FPIA (Fluorescence Polarization Immunoassay) method with an analyser, AxSYM of ABBOTT company. We divided the patients into 3 groups according to peak and trough levels.

Together 13 (19%) patients had high trough concentrations and optimal peak concentrations. Only 6 (9%) patients had optimal trough and peak levels in the first measurement of plasma concentrations. The third group included 49 patients (72%). These patients had optimal trough levels and low peak levels in the first measurement. 34 patients of the third group (28 males, 6 females) had optimal peak levels after adjustment of dosage in the second measurement. 15 patients, only males did not reach optimal peak levels even after adjustment of dosage in the second measurement.

The patients with low peak levels of gentamicin are more frequent than patients with toxic adverse effects in clinical practice. Especially, these are the patients with higher value of body weight and following increased pharmacokinetic parameters: creatinine clearance, total volume of distribution, total clearance and elimination rate constant. The clinical pharmacists have to adjust dosage regimens, especially according to Therapeutic drug monitoring (TDM) and clinical experience. The results of the study have confirmed that the clinical pharmacists must adjust dose regimen not only for patients who require reduced doses but more often for patients who require higher doses than are commonly used in clinical practice. These patients are at risk of underdosing of aminoglycoside antibiotics.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • BERTINO, J., S., Jr. - RODVOLD, K., A., DESTACHE, C., J.: Cost consideration in therapeutic drug monitoring of aminoglycosides. Clin Pharmacokinet, 26, 1, 1994, p. 71 - 81.

  • ROBERTS, J., A. - PATERSON, D., L.- MARTIN, J., H.: Therapeutic drug monitoring of antimicrobials. Br J Clin Pharmacol, 73, 1, 2012, p. 27 - 36.

  • CONNORS, J., E. - DIPIRO J., T. - SISLEY J., F.: Use of serum concentration in surgical patients. Am J Surg 156, 1, 1988, p. 68 - 76.

  • MIGNAVAL, F. - FONTAINE, P., A. - RICHÉ, A. - NOWAK, C. - CANCEL, D. - LEMAITRE, F.: A Priori prediction of gentamicin peak concentrations: Use of a simple and practical tool. PatholBiol (Paris) 59, 2, 2011, p. 79 - 82.

  • VARON, J. - MARIK, P.: Management of the Obese Critically Ill Patient. Crit Care Clin 17, 1, 2001, p. 187 - 200.

  • ROBERT, S. - ZAROWITZ, B.: Is there a reliable index of glomerular filtration rate in critically ill patients? DICP Ann Pharmacother 25, 2, 1991, p. 169 - 178.

  • SAWYER W., T. - CANADAY, B., R. - POE, T., E.: Variables affecting creatinine prediction. Am J Hosp Pharm 40, 12, 1983, p. 2175 - 90.

  • EVANS, W., E -OELRICH, M. - HOLTZ, D., W.: Therapeutic Drug Monitoring. Clinical Guide. 2 ed. Wiesbaden, Germany. ABBOTT Laboratory, Diagnostic Division, 1994, 160 p.

  • MURPHY, J., E.: Clinical Pharmacokinetics. 4th edition Bethesda, Maryland: American Society Health - System Pharmacists, Publishing, 2008, p. 463.

  • DESOKY, E., E. - KLOTZ, U.: Value, limitations and clinical impact of therapeutic drug monitoring in adults. Drug Invest 6, 3, 1993, p. 127 -136.

  • THOMSON, A., H. - DUNCAN, N. - SILVERSTEIN, B. - ALCOCK, S. - JODRELL, D.: Development of guide lines for gentamicin dosing. J Antimicrob Chemother 38, 5, 1996, p.885 - 893.

  • GÖBOÖVÁ, M. - MAGULOVÁ, L.: Use of TDM for optimal gentamicin therapy. Acta Chemother 10, 4-5, 2001, p.89 - 93.

  • MAGULOVÁ, L. - VIRÁG, Ľ. - GÖBOÖVÁ, M.: Interpretation of results of therapeutic monitoring levels of gentamicin. (In Slovak). Acta Chemother 16, 5, 2006, p. 49 - 50.

  • ISMAIL, R. - SARRRIFF, A. - ABDUL RAHMAN, A., F.: Therapeutic drug monitoring for gentamicin in Hospital Universiti Sains Malaysia. Med J Malaysia, 45, 1, 1990, p. 57-64.

  • ISMAIL, R. - HAQ, A., H. - RAHMAN, A., F.: Therapeutic drug monitoring of gentamicin: a 6-year follow-up audit. J Clin Ther 22, 1, 2001, p. 21-25.

  • LAM, F., Y., W. - Banerji, S. - Hatfield, C. - Talbert, R., L.: Principles of drug administration in renal insufficiency. Clin Pharmacokinetic 32, 1, 1997, p. 30 - 57.

  • PAI, M., P. - NAFZIGER, A., N.- BERTINO, J., S.: Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother 55, 9, 2011, p. 4006 - 4011.

  • LEYKIN, Y. - MIOTTO, L. - PELLIS, T.: Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol 25, 1, 2011, p. 27 -36.

  • PAI, M., P.: Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis. 17, 5, 2010, p. 53 - 62.

  • SALAZAR, D., E. - CORCORAN, G., B.: Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat free body mass. Am J Med 84, 6, 1988, p. 1053 - 1060.

  • DHILLON, S. - KOSTRZEWSKI, A.: Clinical Pharmacokinetics. 1st edition London, Chicago: Pharmaceutical Press, Publishing, 2006, p. 262.

  • TOD, M., M. - PADOIN, C. - PETITJEAN, O.: Individualising aminoglycosides dosage regimens after therapeutic drug monitoring: simple or complex pharmacokinetic methods? Clin Pharmacokinet 40, 11, 2001, p. 803 - 814.


Journal + Issues