Population Pharmacokinetics of Vancomycin in Iranian Paediatric Patients
S. Rezaee(1), T. Safarnavadeh(2), H. Khalili(2), S. Dashti(2), K. Daneshjoo(3), S. Sadray(4)
(1)Department of Pharmaceutics, School of Pharmacy, Jundishapur University of Medical Sciences, Ahwaz, Iran; (2) Department of Pharmacotherapy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; (3) Department of Pediatric Infectious Diseases, Imam Khomeini Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran (4) Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Objectives: The pharmacokinetic profile of vancomycin (VCM) differs between paediatrics and adult patients, therefore understanding VCM pharmacokinetics in paediatric patients is needed for planning of individualized optimal VCM dosage. The main goal of this study was to develop a pharmacokinetic model for vancomycin in a population of Iranian paediatric patients.
Methods: Sparse serum samples (n = 100) were collected prospectively from 62 paediatric patients aged one month to 14 years( 3.8±4.2 years) in the weight range of 2.6 to 48 (13.7±11.6) kg . Serum samples were assayed for VCM concentration using fluorescence polarization immunoassay technique. A one-compartment PK model with zero order input was used. Population pharmacokinetic analysis was carried out using Monolix 2.4 software. For 49 patients (who had complete covariate data set), the influence of patients' characteristics on VCM PK parameters was assessed using both graphical approaches and Multivariate Adaptive Regression Splines method.
Results: The values of PK parameters (inter-individual variability %) obtained from the base model are: CL=0.13(380%) L/kg/hr and V=1.28(70%). Creatinine clearance (calculated by Schwartz method) seemed to be the only covariates that influence VCM clearance; however it could not decrease the variability in the vancomycin clearance significantly.
Conclusions: Large inter individual variability observed especially in vancomycin clearance could be due to heterogeneous nature of the study population especially with regard to the age range. Weight did not influence vancomycin clearance and volume of distribution as a significant covariate because its effect has been already taken into account by using the weight normalized doses in calculations. However, the parameters derived by the base model have the potential to be used as prior of Bayesian estimation for individualization of the vancomycin dosage regimen.