Vancomycin Pharmacokinetic Parameters in Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

Abstract

Background: Vancomycin is used abundantly in patients undergoing HSCT, especially during neutropenic fever. Despite its widespread use little is known about vancomycin pharmacokinetics in HSCT patients. We conducted this study to investigate vancomycin pharmacokinetic parameters in our HSCT patients and to evaluate current dosing regimen based on trough vancomycin concentrations measurement.

Methods: Vancomycin serum concentration at steady-state was determined prospectively in 46 adult HSCT patients who received vancomycin as empirical treatment of neutropenic fever. Individual steady-steady pharmacokinetic parameters were also determined in 20 patients who had two vancomycin levels from an administered dose, assuming one-compartment model. Acute kidney injury was also evaluated in our patients during vancomycin therapy.

Results: Mean (±SD) apparent volume of distribution (L/kg) and clearance (mL/min) were 0.6 (± 0.33) and 109.7 (± 57.5) respectively. With mean (±SD) total daily dose of vancomycin 31.9 (±10.5) mg/kg/day that was administered, more than 90% of measured vancomycin trough concentrations were outside the range of 15-20 mg/L and 54.3% of patients had trough concentrations below 10 mg/L. Of 46 patients, 21 patients (45.7%) developed acute kidney injury (AKI) during vancomycin therapy; among them 19 patients were receiving nephrotoxic drug(s) concomitantly.

Conclusion: Current vancomycin dosage regimen could not lead to recommended therapeutic serum concentrations in our patients. Large variation in vancomycin pharmacokinetic parameters observed among patients of this study along with difference of vancomycin pharmacokinetics in our study and other similar studies further explain the need for therapeutic drug monitoring and individualization of vancomycin dosing.

Keywords: Hematopoietic stem cell transplantation; Neutropenic fever; Pharmacokinetic parameters; Vancomycin.