Effect of Augmented Renal Clearance and Febrile Neutropenia on Initial Trough Level and Clearance of Teicoplanin.

Abstract

Background: Augmented renal clearance (ARC) and febrile neutropenia (FN) increase drug clearance primarily through glomerular filtration. In this study, we evaluated the influence of ARC and FN on dose-normalized trough concentration (C/D) and/or clearance of teicoplanin (TEIC) by comparing C/D between patients with ARC and non-ARC, and C/D and clearance between patients with FN and non-FN.

Methods: This retrospective, single-center, observational cohort study enrolled 309 patients who received intravenous injections of TEIC between July 2016 and September 2021. Of the 94 patients who met the selection criteria, 25 satisfied the ARC definition, and 31 satisfied the FN definition. Using the Chronic Kidney Disease Epidemiology Collaboration formula, ARC was defined as an estimated glomerular filtration rate of 96.5 mL/min/1.73 m2 or higher. FN was defined as an axillary temperature 37.5°C or higher and neutrophil count of less than 500/μL. TEIC clearance was estimated using a population pharmacokinetic model for adult Japanese patients with Bayesian estimation.

Results: Compared with the non-ARC group (n = 69), the ARC group (n = 25) had a significantly lower first trough concentration (P = 0.014) and lower C/D (P = 0.009). By contrast, the FN (n = 31) and non-FN (n = 63) groups did not differ significantly in the first trough concentration, C/D, or clearance (P = 0.294, 0.945, and 0.337, respectively). Forced-entry multiple regression analysis identified ARC as the only independent factor associated with C/D (P = 0.001).

Conclusions: A higher TEIC loading dose may be required for patients with ARC, regardless of the presence or absence of FN.