Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl


Preferences help
enabled [disable] Abstract
Number of results


2014 | 9 | 3 | 485-490

Article title

Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates


Title variants

Languages of publication



Gentamicin is readily used for suspected or proven sepsis in neonates, yet it shows considerable inter-individual pharmacokinetic variability, which limits achievements of therapeutic levels. Hence, the aim of this study was to compare peak and trough gentamicin concentrations according to dosing regimen, to evaluate pharmacokinetic parameters, and to consider adjustments of dosing regimen. Babies with infection were treated with 1 h infusion, and daily dose of 5 or 7.5 mg/kg depending on the age. Patients were randomized into two groups: I - dosing interval 12 h (n=8), II - 24 h (n=11). Two steady-state blood samples were obtained. Pharmacokinetic parameters were calculated using one-compartment model. The results showed a difference (p<0.05) in peak gentamicin concentrations between the groups, and tendency of lower trough levels in the group II. Calculated pharmacokinetic parameters included the volume of distribution (Vd) 0.52±0.47 l/kg, clearance (CL) 0.055±0.036 l/hkg and a half-life (t1/2) of 6.89±3.21 h. Based on the method for dosing regimen adjustments, there was a need to extend dosing interval to 36 h in 6 patients










Physical description


1 - 6 - 2014
8 - 7 - 2014


  • Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
  • Institute for Mother and Child Health Care of Serbia “Dr Vukan Čupić”, Belgrade, Serbia
  • Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
  • Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
  • Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade School of Medicine, Belgrade, Serbia


  • [1] British National Formulary for Children (BNFC) 2013–2014. London: British Medical Association, the Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group. London
  • [2] Touw D.J., Westerman E.M., Sprij A.J., Therapeutic drug monitoring of aminoglycosides in neonates, Clin. Pharmacokinet, 2009, 48, 71–88 http://dx.doi.org/10.2165/00003088-200948020-00001[Crossref]
  • [3] Bauer L., Aminoglycoside Antibiotics, In: Applied Clinical Pharmacokinetics, 2nd ed., McGraw Hill, New York, 2008, 97–206
  • [4] Rao S.C., Srinivasjois R., Hagan R., Ahmed M., One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates, Cochrane Database Syst Rev, 2010, CD005091 [WoS]
  • [5] Barza M., Ioannidis J.P., Cappelleri J.C., Lau J., Single or multiple daily doses of aminoglycosides: a meta-analysis, BMJ, 1996, 312, 338–345 http://dx.doi.org/10.1136/bmj.312.7027.338[Crossref]
  • [6] Croes S., Koop A.H., van Gils SA., Neef C., Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring, Eur J Pharm Sci, 2012, 45, 90–100 http://dx.doi.org/10.1016/j.ejps.2011.10.022[Crossref][WoS]
  • [7] Pacifici G.M., Clinical pharmacokinetics of aminoglycosides in the neonate: a review, Eur J Clin Pharmacol, 2009, 65, 419–427 http://dx.doi.org/10.1007/s00228-008-0599-y[WoS][Crossref]
  • [8] Anderson G.D., Developmental pharmacokinetics, Semin Pediatr Neurol, 2010, 17, 208–213 http://dx.doi.org/10.1016/j.spen.2010.10.002[Crossref]
  • [9] Mannan M.A., Shahidulla M., Salam F., Alam M.S., Hossain M.A., Hossain M., Postnatal development of renal function in preterm and term neonates, Mymensingh Med J, 2012, 21, 103–108 [PubMed]
  • [10] van den Anker J.N., Allegaert K., Individualized dosing of aminoglycosides in neonates: mission accomplished or work in progress?, Eur J Clin Pharmacol, 2009, 65, 1159–1160 http://dx.doi.org/10.1007/s00228-009-0688-6[WoS][Crossref]
  • [11] Burton M., Shaw L., Schentag J., Evans W., Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring, 4th ed., Lippincott Williams & Wilkins, London, 2006
  • [12] Sawchuk R.J., Zaske D.E., Cipolle R.J., Wargin W.A., Strate R.G., Kinetic model for gentamicin dosing with the use of individual patient parameters, Clin Pharmacol Ther, 1977, 21, 362–369
  • [13] Vervelde M.L., Rademaker C.M., Krediet T.G., Fleer A., van Asten P., van Dijk A., Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen, Ther Drug Monit, 1999, 21, 514–519 http://dx.doi.org/10.1097/00007691-199910000-00004[Crossref]
  • [14] Lundergan F.S., Glasscock G.F., Kim E.H., Cohen R.S., Once-daily gentamicin dosing in newborn infants, Pediatrics, 1999, 103, 1228–1234 http://dx.doi.org/10.1542/peds.103.6.1228[Crossref]
  • [15] Nielsen E.I., Sandstrom M., Honore P.H., Ewald U., Friberg L.E., Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study, Clin Pharmacokinet, 2009, 48, 253–263 http://dx.doi.org/10.2165/00003088-200948040-00003[WoS][Crossref]
  • [16] Cars O., Odenholt-Tornqvist I., The post-antibiotic sub-MIC effect in vitro and in vivo, J Antimicrob Chemother, 1993, 31, 159–166 http://dx.doi.org/10.1093/jac/31.suppl_D.159[Crossref]
  • [17] Stolk L.M., Degraeuwe P.L., Nieman F.H., de Wolf M.C., de Boer A., Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates, Ther Drug Monit, 2002, 24, 527–531 http://dx.doi.org/10.1097/00007691-200208000-00011[Crossref]
  • [18] Weber W., Kewitz G., Rost K.L., Looby M., Nitz M., Harnisch L., Population kinetics of gentamicin in neonates, Eur J Clin Pharmacol, 1993, 44, S23–25 http://dx.doi.org/10.1007/BF01428387[Crossref]
  • [19] Jensen P.D., Edgren B.E., Brundage R.C., Population pharmacokinetics of gentamicin in neonates using a nonlinear mixed-effects model, Pharmacotherapy, 1992, 12, 178–182
  • [20] Knight J.A., Davis E.M., Manouilov K., Hoie E.B., The effect of postnatal age on gentamicin pharmacokinetics in neonates, Pharmacotherapy, 2003, 23, 992–996 http://dx.doi.org/10.1592/phco.23.8.992.32877[Crossref]

Document Type

Publication order reference


YADDA identifier

JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.