Pharmacokinetics of vancomycin in extremely obese patients with suspected or confirmed Staphylococcus aureus infections

Abstract

Study objective: To estimate vancomycin pharmacokinetic parameters and dosing requirements in a cohort of extremely obese patients.

Design: Prospective pharmacokinetic study.

Setting: Acute care community teaching hospital.

Patients: Thirty-one extremely obese (body mass index [BMI] ≥ 40 kg/m(2) ) men and women who were receiving vancomycin for at least 3 days for suspected or confirmed Staphylococcus aureus infections.

Measurements and main results: Population pharmacokinetic parameters were used to determine vancomycin doses that target trough concentrations of 10-20 μg/ml. Three serum vancomycin concentrations (peak, trough, and midpoint) were measured at steady state for each patient. A 24-hour urine collection was performed to determine creatinine clearance (Clcr ). A one-compartment intravenous infusion model was fit to the serum vancomycin concentrations by using nonlinear mixed-effects modeling. Covariates that affect the volume of distribution and clearance of vancomycin were explored. Patients had a median weight of 147.9 kg, BMI of 49.5 kg/m(2) , and a Cockcroft-Gault Clcr of 124.8 ml/minute/1.73 m(2) . Patients received a median vancomycin dose of 4000 mg/day that provided a median 24-hour area under the concentration-time curve (AUC) of 582.9 (interquartile range 513.8-726.2) mg·hour/L. The population mean volume of distribution was 0.51 L/kg, and clearance was 6.54 L/hour. Simulations indicated that 4000-5000 mg/day of vancomycin provided ≥ 93% probability 24-hour AUC/minimum inhibitory concentration (MIC) ratio of ≥ 400 for an MIC of 1 μg/ml.

Conclusion: Total body weight and Clcr influenced volume of distribution and vancomycin clearance, respectively. Vancomycin can be initiated in extremely obese patients at dosages determined based on renal function and pharmacokinetic parameter estimates from this study. Vancomycin serum concentrations should be monitored to ascertain attainment within the therapeutic range.

Keywords: NONMEM; obesity; peak; pharmacokinetics; trough; vancomycin.