Esther J.H. Janssen (1), Pyry A.J. Välitalo (1), Roosmarijn F. de Cock (1), Karel Allegaert (2), Johannes N. van den Anker (3,4), Meindert Danhof (1), Catherijne A.J. Knibbe (1,5)
(1) Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands; (2) Neonatal Intensive Care Unit, University Hospital Leuven, Leuven, Belgium; (3) Department of Pediatric Intensive Care, Erasmus MC – Sophia Children’s Hospital, Rotterdam, the Netherlands; (4) Division of Pediatric Clinical Pharmacology, Children’s National Medical Center, Washington, DC, USA; (5) Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands
Objectives: Despite many reports on the pharmacokinetics of vancomycin in children, target concentrations of vancomycin in daily practice are difficult to reach. Recently, the developmental changes in glomerular filtration (GFR) mediated elimination of gentamycin, tobramycin and vancomycin from neonates to adulthood were characterised [1]. In the present study, the GFR model of vancomycin [1] was used to evaluate vancomycin exposure in children upon commonly used dosing algorithms. Ultimately, a model-based dosing regimen that will lead to predictable exposure across children is derived.
Methods: Concentration-time profiles were simulated using the GFR model of vancomycin [1] in typical children aged 1 month-18 years. Both intermittent and continuous dosing regimens were simulated according to British National Formulary for children, Dutch Children’s Formulary, IDSA, National Neonatal Formulary and other publications [2-4]. Target trough concentrations were 10-15 mg/L or 15-20 mg/L after intermittent dosing. For continuous dosing, target concentrations were 15-25 mg/L. In all cases, the concentration should not exceed 40 mg/L.
Results: Children aged <1 year were exposed to a large variety in concentrations for the different intermittent and continuous dosing regimens. For children older than 1 year, vancomycin exposure seems within the target concentration when dosed 60 mg/kg/day. Steady state concentrations were reached between 31 and 53 hours of dosing for children aged >1 year and a 1 month old infant, respectively, suggesting the need for a loading dose in particularly the youngest age ranges.
Conclusions: On the basis of this simulation study, a model-based dosing algorithm is proposed that will result in optimal vancomycin concentrations after either intermittent or continuous dosing for children aged < 1 year. For children aged 1 year or older, a maintenance dose of 60 mg/kg/day seems appropriate. A clinical study is needed to demonstrate the prospective value of this dosing regimen.
References:
[1] De Cock RFW, Allegaert K, Brussee JM, Sherwin CMT, Mulla H, Hoog M de, et al. Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration. Pharm Res. 2014; In press
[2] McKamy S, Chen T, Lee M, Ambrose PJ. Evaluation of a pediatric continuous-infusion vancomycin therapy guideline. Am J Health Syst Pharm. 2012 Dec 1;69(23):2066–71
[3] Oudin C, Vialet R, Boulamery A, Martin C, Simon N. Vancomycin prescription in neonates and young infants: toward a simplified dosage. Arch Dis Child Fetal Neonatal Ed. 2011 Sep;96(5):F365–70
[4] Pawlotsky F, Thomas A, Kergueris MF, Debillon T, Roze JC. Constant rate infusion of vancomycin in premature neonates: a new dosage schedule. Br J Clin Pharmacol. 1998 Aug;46(2):163–7
Reference: PAGE 23 (2014) Abstr 3170 [www.page-meeting.org/?abstract=3170]
Poster: Drug/Disease modeling - Paediatrics