Mangues MA1, Trocóniz IF2, Soy D3, Alba G1, GarcÃa M1, Ginovart G4.
1) Pharmacy Service, Hospital Sant Pau, Barcelona, Spain; 2) Department of Pharmacy, Faculty of Pharmacy, University of Navarra, Pamplona; 3) Pharmacy Service, Clinic Hospital, Barcelona; 4) Unit of Neonatology, Hospital Sant Pau, Barcelona.
Aim: The aim of this study was to develop a population pharmacokinetic model for gentamicin in neonates with emphasis in the study of the relationship between plasma clearance of gentamicin and serum creatinine and creatinine clearance.
Methods: Pharmacokinetics of gentamicin was prospectively studied in 117 neonates. Inclusion criteria were: (i) gestational age (ge) between 26 and 42 weeks, (ii) postnatal age (pe) less than 15 days. Gentamicin was administered as a 30 min. iv. infusion at doses of 2.5 mg/kg every 24 h. (ge£ 31 weeks), 18 h. (32<ge£ 34 weeks), or 24 h. (ge>34 weeks). Gentamicin plasma concentrations were determined by fluorescence polarization immunoassay. The following covariates were recorded: ge, pe, sex, serum creatinine, height, birth weight (bwt), weight (wt) and creatinine clearance (Clcrea). Plasma drug concentration vs time data was analyzed using the population approach with NONMEM.
Results: A total of 306 (mean of 2.6 concentrations/patient) plasma concentrations were used during the analysis. The basic model was a one compartment model, with interindividual variability terms modelled exponentially and associated to volume of distribution (V), and plasma clearance (Cl). Intraindividual variability was described using an additive error model. Clcrea, and bwt were the covariates selected for Cl, and wt the covariate selected for V. Parameter vs covariate relationship were finally modelled as follows: Cl=Cl*(bwt/2.1)*(Clcrea/18.8); V=V*(wt/2.1). Including selected covariates in the final model a 15 and 65% reduction in unexplained interindividual variability was found for V and Cl, respectively.
Conclusions: The main finding was that Clcrea resulted a better predictor of the gentamicin plasma clearance of the neonates than gestational age. This result suggests that the values of serum creatinine obtained during the first days of life reflect the renal function of the neonate.
Reference: PAGE 9 () Abstr 111 [www.page-meeting.org/?abstract=111]
Poster: poster