Area under the Curve-Based Dosing of Vancomycin in Critically Ill Patients Using 6-Hour Urine Creatinine Clearance Measurement.

Abstract

Background: The area under the curve- (AUC-) guided vancomycin dosing is the best strategy for individualized therapy in critical illnesses. Since AUC can be calculated directly using drug clearance (CL_van), any parameter estimating CL_van will be able to achieve the goal of 24-hour AUC (AUC_24 h). The present study was aimed to determine CL_van based on 6-hour urine creatinine clearance measurement in critically ill patients with normal renal function.

Method: 23 adult critically ill patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min who received vancomycin infusion were enrolled in this pilot study. Vancomycin pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model provided by MONOLIX software using stochastic approximation expectation-maximization (SAEM) algorithm. Correlation of CL_van with the measured creatinine clearance in 6-hour urine collection (CL_6 h) and estimated creatinine clearance by the Cockcroft-Gault formula (CL_CG) was investigated.

Results: Data analysis revealed that CL_6 h had a stronger correlation with CL_van rather than CL_CG (r = 0.823 vs. 0.594; p < 0.001 vs. 0.003). The relationship between CL_van and CL_6 h was utilized to develop the following equation for estimating CL_van: CL_van (mL/min) = ─137.4 + CL_6 h (mL/min) + 2.5 IBW (kg) (R ²  = 0.826, p < 0.001). Regarding the described model, the following equation can be used to calculate the empirical dose of vancomycin for achieving the therapeutic goals in critically ill patients without renal impairment: total daily dose of vancomycin (mg) = (─137.4CL_6-h (mL/min) + 2.5 IBW (kg)) × 0.06 AUC_24 h (mg.hr/L).

Conclusion: For AUC estimation, CL_van can be obtained by collecting urine in a 6-hour period with good approximation in critically ill patients with normal renal function.