Population pharmacokinetics predicts vancomycin empiric dose frequency in acute brain injury
Population pharmacokinetics accurately predicts the empiric dose frequency of vancomycin in patients with acute brain injury, as shown by the small clinical difference in population and patient-specific elimination rate constants, according to a new study.
The analysis included 158 patients (aged ≥18 years) with acute brain injury. Mean population-predicted elimination rate constant was larger by 0.0211 h−1 (95 percent CI, −0.028 to −0.015) in the test of paired differences between the mean population-predicted and patient-specific elimination rate constants. The difference between the corresponding half-lives showed a 1.01-hour (0.7–1.3) shorter mean population-predicted half-life.
Vancomycin at a mean initial dose of 15.4±2.2 mg/kg, with an average frequency of 12±1.1 hours, was administered. The average trough concentration at steady state was 9.9±4.9 µg/mL.
This single-centre, retrospective cohort study, which was conducted after institutional review board approval at Virginia Commonwealth University Health System, sought to determine whether population pharmacokinetics accurately predicted vancomycin empiric dose frequency in patients with acute brain injury. Data were then obtained from this population.
The difference in the elimination rate constant of vancomycin between population-predicted pharmacokinetics and patient-specific pharmacokinetics was the primary outcome.
“Vancomycin is a glycopeptide antibiotic that is primarily cleared by renal elimination,” the investigators said. “Patients with acute brain injury often exhibit augmented renal clearance which has been associated with subtherapeutic vancomycin concentrations.”
Current guidelines recommend empiric doses of vancomycin 15–20 mg/kg administered by intermittent infusion every 8–12 hours in patients with normal kidney function. In addition, the recommended trough concentration is 15–20 mg/L as a therapeutic goal for adult patients with severe infections. [Eur J Drug Metab Pharmacokinet 2018;43:259-268]