Study On Pharmacokinetics Of Vancomycin In ICU Patients

Background:The Cumulative Fraction of Response (CFR) and optimization of Dosage regiment in Vancomycin clinical therapeutic usage were focused as a result of increasing of MRSA infections and appearance of VISA and VRSA, and also the Vancomycin MIC creep. But critical ill patients have an alternative pharmacokinetic progressing because of their disease or special therapeutic measures. A PK-PD modeling guiding evaluation of vancomycin is necessary to optimize dosage regiments, as well as improving CFRs and preventing drug-resistant.Object:Learning the pharmacokinetics characteristics of Vancomycin in critical ill patients and evaluating in a PK-PD model. This should be enveloping some dosage advices for Vancomycin usage in critical care patients.Method:Internalized ICU patients from March 2010 to February 2011 which accepted Vancomycin therapy, measured their serum creatinine (Scr) and endogenous creatinine clearance rate (CLCR). All subjects were grouped into normal renal function group and renal impairment group due to CLCR. Patients'plasma samples were collected after administration and analyzed by FPIA method using Abbott AxSYM Vancomycin_Ⅱsystem. Pharmacokinetic parameters were calculated by DAS2.0 processing. A PK-PD modeling guiding evaluation was taken which contents PK parameters, PD parameters, and patients'information. The experimental data was statistical analysis by PASW v18 statistical analysis software package.Results:There are 12 ICU patients were internalized and 137 blood samples were collected for TDM of Vancomycin. The pharmacokinetic process of critical ill patients is following a multiple compartment model. If calculated in the two compartments model, the pharmacokinetic parameters are correlated with patients' age and renal creatinine clearance (CLCR). The internalized subjects have a faster distribution phase than normal population pharmacokinetics. The pharmacokinetics parameters of the 12 patients are following:t1/2α=0.36h, Vd=0.38L/kg, t1/2β=9.85h, CL=0.063L/min. In normal renal function group with CLCR> 90mL/min, t1/2α=0.24h, t1/2β=7.71 h, Vd=0.26L/kg, CL=0.067L/min; which are slower in renal dysfunction group with parameters of t1/2α=0.45h, t1/2β=11.38h, Vd=0.46L/kg, CL=0.060L/min. A dosage based CLCR following the dosing curve should be enough to maintain an effective trough serum vancomycin concentration of 15-20mg/L. But this dosage is too low for an initial treatment, which suggests a loading dose to facilitate rapid attainment of target trough serum vancomycin concentration. A loading dose of 25-30mg/kg calculated by acute body weight was suggested by new guidelines, and also an added common dosage in the first day should be administrated as an initial therapy.Conclusion:Pharmacokinetic parameters in intensive patients are different with normal population. Intensive patients have a hypermetabolism and high hemodynamic state which result a faster distribution phase. The main factors influencing vancomycin pharmacokinetic parameters are age and renal function. CLCR should be employed as a predictor for dosage and TDM. A loading dose is suggested to facilitate rapid attainment of target trough serum vancomycin concentration.