Pharmacokinetics of Subcutaneous and Intravenous Ceftriaxone in an Older Population: The PhASAge Study.

Abstract

Background: Ceftriaxone is frequently administered subcutaneously in France, especially in older patients, although this practice is currently off-label. This work aims to describe the pharmacokinetics (PK) and pharmacodynamics (PD) and tolerance of ceftriaxone administered by intravenous and subcutaneous routes in older patients.

Methods: Patients aged ≥65 years receiving intravenous or subcutaneous ceftriaxone 1 g every 24 hours were included. Steady-state plasma concentrations of ceftriaxone were measured. Based on intravenous and subcutaneous ceftriaxone concentrations and 24-hour area under the concentration-time curve (AUC), a population PK model was developed for probability of target attainment (PTA) analysis. Local and systemic adverse events (AEs) were collected.

Results: Data from 47 patients (24 in subcutaneous and 23 in intravenous groups) were analyzed. No between-group difference was observed in demographic and biological characteristics, ceftriaxone trough concentrations, or AUC. Bioavailability of subcutaneous ceftriaxone was estimated at 99% by population modeling. The PTA associated with subcutaneous administration were similar to or slightly better than that of the intravenous route. A dosing regimen of 1 or 2 g every 24 hours was associated with acceptable PTA and a low risk of overexposure in patients with normal or moderately altered renal function. Tolerance was assessed on 149 infusions (67 intravenous and 82 subcutaneous). One local AE (1.5%) was reported in the intravenous group versus 11 local AEs (mainly edema) in the subcutaneous group (13%), all transient and nonsevere.

Conclusions: Subcutaneous administration of ceftriaxone was associated with PK/PD and dosage requirements comparable to those of intravenous administration, supporting the use of subcutaneous ceftriaxone in older patients.