आणविक और आनुवंशिक चिकित्सा

The Pharmacokinetics, Optimal Dose and Therapeutic Monitoring of Vancomycin in Severe Burn Patients

Abstract

Chien-Chih W, Li-Feng H, Jann-Tay W, Shu-Wen L and Eng-Kean Y

Objectives: This paper investigated the pharmacokinetic (PK) change, optimal dose and therapeutic monitoring method of vancomycin in severe burns.
Method: This is a retrospective, matched cohort study. Nine burn patients were included, and each individual was matched with a control critically ill patient. Vancomycin concentrations were analyzed using the first order pharmacokinetic principles to calculate elimination rate constant (K), half-life (t1/2), volume distribution (Vd), total body clearance (CLvancomycin) and the 24-hour area under the curve (AUC24 h). Population PK analysis and Monte Carlo simulation was used to investigate optimal dose.
Results: The mean burn area of the burn group and age was 60% and 20 years-old respectively. The loading dose and daily maintenance dose was significantly higher in burn group than that in control group. Vancomycin clearance was significantly higher (p<0.05) in burns patients when compared to control patients. CLCr (creatinine clearance) was not significantly correlated to CLvancomycin (vancomycin clearance) in both groups. Ctrough (serum trough concentration) was significantly correlated with AUC24h in the control group (r=0.98, R2=0.96, p<0.01), but not in the burn group (r=0.63, R2=0.40, P=0.07). Daily dose of 5000 mg of vancomycin could achieve 90% probability of target attainment if target was AUC24h /MIC (minimum inhibitory concentration)>400.
Conclusion: Two steady state concentrations but not Ctrough is an appropriate reference for vancomycin therapeutic monitoring. A daily dose of at least 5000 mg is suggested in severe burn patients with normal renal function (CLCr>90 mL/min).