Allison Oswalt1, Anny-Claude Joseph2, Adam Sima2, Lisa Kurczewski1. 1. 1 Department of Pharmacy, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA. 2. 2 Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA.
Abstract
BACKGROUND: Vancomycin is a glycopeptide antibiotic that is primarily cleared by renal elimination. Patients with acute brain injury often exhibit augmented renal clearance which has been associated with subtherapeutic vancomycin concentrations. OBJECTIVE: To determine whether population pharmacokinetics accurately predict vancomycin empiric dose frequency in patients with acute brain injury. METHODS: This was a single-center, retrospective cohort study conducted following institutional review board approval at Virginia Commonwealth University Health System. Data were collected from patients 18 years of age or older admitted with acute brain injury. The primary outcome was the difference in the elimination rate constant of vancomycin between population predicted pharmacokinetics and patient-specific pharmacokinetics. RESULTS: A total of 158 patients were included in the analysis. A test of the paired differences between the mean population predicted and patient-specific elimination rate constants showed that the mean population predicted elimination rate constant was larger by 0.0211 h-1 (95% confidence interval [CI]: -0.028 to -0.015). The difference between the mean population predicted and patient-specific half-lives showed that the mean population predicted half-life was shorter by 1.01 hours (95% CI: 0.7-1.3). Vancomycin was administered at a mean initial dose of 15.4 mg/kg (standard deviation [SD] = 2.2), with an average frequency of 12 hours (SD = 1.1). The average trough concentration at steady state was 9.9 µg/mL (SD = 4.9). CONCLUSIONS: The small clinical difference in population and patient-specific elimination rate constants demonstrates that population pharmacokinetics may be an accurate empiric dosing strategy for determining vancomycin dose frequency in patients with acute brain injury.
BACKGROUND: Vancomycin is a glycopeptide antibiotic that is primarily cleared by renal elimination. Patients with acute brain injury often exhibit augmented renal clearance which has been associated with subtherapeutic vancomycin concentrations. OBJECTIVE: To determine whether population pharmacokinetics accurately predict vancomycin empiric dose frequency in patients with acute brain injury. METHODS: This was a single-center, retrospective cohort study conducted following institutional review board approval at Virginia Commonwealth University Health System. Data were collected from patients 18 years of age or older admitted with acute brain injury. The primary outcome was the difference in the elimination rate constant of vancomycin between population predicted pharmacokinetics and patient-specific pharmacokinetics. RESULTS: A total of 158 patients were included in the analysis. A test of the paired differences between the mean population predicted and patient-specific elimination rate constants showed that the mean population predicted elimination rate constant was larger by 0.0211 h-1 (95% confidence interval [CI]: -0.028 to -0.015). The difference between the mean population predicted and patient-specific half-lives showed that the mean population predicted half-life was shorter by 1.01 hours (95% CI: 0.7-1.3). Vancomycin was administered at a mean initial dose of 15.4 mg/kg (standard deviation [SD] = 2.2), with an average frequency of 12 hours (SD = 1.1). The average trough concentration at steady state was 9.9 µg/mL (SD = 4.9). CONCLUSIONS: The small clinical difference in population and patient-specific elimination rate constants demonstrates that population pharmacokinetics may be an accurate empiric dosing strategy for determining vancomycin dose frequency in patients with acute brain injury.
Authors: IfeanyiChukwu O Onor; Alison Neuliep; Kieu Anh Tran; Jennifer Lambert; Christopher J Gillard; Fatima Brakta; Michael C Ezebuenyi; Kirbie St James; John I Okogbaa; Robbie A Beyl Journal: Drugs R D Date: 2020-06