Population Pharmacokinetics Of Vancomycin In Tunisian Patients
N. Jebabli, H. El jebari, E. Gaïes, I. Salouage, S.Trabelsi, M. Lakhal, A. Klouz
Service de Pharmacologie Clinique Centre National de Pharmacovigilance
Objectives: Vancomycin (VCM) is a glycopeptide antibiotic generally used for the treatment of gram-positive infections. For individualized optimal VCM dosage we develop a pharmacokinetic model for VCM in a population of Tunisian patients.
Methods: The population pharmacokinetics of VCM was investigated in 202 patients aged eight month to 64 years (40±20 years), following sepsis. Dose of VCM was varied between 0.04 to 6 g per day with median equal to 1.5 g and was administered by intravenous infusion. Patients benefited from two plasma samples: T0 immediately before VCM infusion and Tmax: 60 minute following completion of VCM infusion. The serum concentrations of VCM were measured by a fluorescence polarization (Axym® Abbott). The population data set comprised 473 concentration measurements and was analysed using NONMEM®. A one-compartment PK model with zero order input was used. The following clinical factors were tested for their influence on clearance (CL) and volume of distribution (V): sex; age, weight and creatinine clearance. Model comparisons were based on the change in objective function value (OFV).
Results: The values of PK parameters (inter-individual variability %) obtained from the base model are: CL=4.09 (59.3%) L/hr and V=55.10 (320%) L. Covariate selection revealed that total body weight (TBW) affected V, and creatinine clearance influenced VCM clearance. A good correlation was obtained between Bayesian estimated and experimental concentrations (r²=0.84).
Conclusions: The models could be used to estimate appropriate VCM dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application to dosage individualizes using Bayesian approach.
References:
[1] Dolores Santos Buelga, Maria del Mar Fernandez de Gatta, Emma V. Herrera, Alfonso Dominguez-Gil, and Maria Jose Garci. Population Pharmacokinetic Analysis of Vancomycin in Patients with Hematological Malignancies. Antimicrobial Agents And Chemotherapy, Dec. 2005, 49 : 4934-4941
[2] Lamarre P.; Lebel D.; Ducharme M. P. A population pharmacokinetic model for vancomycin in pediatric patients and its predictive value in a naive population. Antimicrobial Agents And Chemotherapy 2000, 44 (2) : 278-282
