2010 - Berlin - Germany

PAGE 2010: Applications- Anti-infectives
Jebabli Nadia

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 




Reference: PAGE 19 (2010) Abstr 1772 [www.page-meeting.org/?abstract=1772]
Poster: Applications- Anti-infectives
Click to open PDF poster/presentation (click to open)
Top