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

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.