Safety, tolerability, and pharmacokinetics of a 2 g subcutaneous dose of ceftriaxone as an alternative to intravenous delivery

TL;DR

This study shows that a 2 g subcutaneous dose of ceftriaxone is safe and has similar effects to intravenous administration in non-critically ill patients.

Contribution

The study provides new evidence on the safety and pharmacokinetics of a 2 g subcutaneous ceftriaxone dose as an alternative to intravenous delivery.

Findings

Subcutaneous ceftriaxone had 95.7% bioavailability with minimal pain and no lasting discomfort.

Pharmacokinetic profiles of subcutaneous and intravenous ceftriaxone were comparable for most common infections.

Target attainment probabilities for subcutaneous and intravenous doses were similar in non-critically ill patients.

Abstract

Subcutaneous delivery of antibiotics is a practical alternative to intravenous administration. Ceftriaxone is commonly used for a variety of infections with limited data on the safety and pharmacokinetics of a 2 g subcutaneous dose. This was a prospective, self-controlled cross-over study in 20 stable inpatients receiving ceftriaxone for their infection. Following an intravenous dose, participants received a single dose of 2 g subcutaneous ceftriaxone, in 50 mL normal saline via gravity feed. Capillary dried blood spots were collected at baseline, 1, 2, 4, 8, and 24 hours following the subcutaneous and intravenous doses. Pain scores and infusion site reactions (edema/erythema) were assessed. Ceftriaxone concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. The highest median (interquartile range) pain score within the first 2 hours following infusion of a subcutaneous dose of 2 g ceftriaxone was 2.5 (1–4). All participants were pain-free 4 hours after the infusion. The estimated bioavailability was 95.7% (95% bootstrap interval 90.3–99.5). Compared with intravenous, subcutaneous administration resulted in lower peak and comparable trough concentrations. The probability of target attainment for free drug concentrations was similar to intravenous administration for most common infections in hospitalized patients. Subcutaneous administration of 2 g ceftriaxone is well tolerated and has a comparable pharmacokinetic profile relative to intravenous dosing in non-critically ill patients with severe infections.

This prospective, self-controlled cross-over design study demonstrates that subcutaneous administration of 2 g ceftriaxone appears safe and well tolerated with a comparable pharmacokinetic profile relative to intravenous dosing in non-critically ill patients with severe infections.

This study was registered at ACTRN12624000692538.

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