Safety, tolerability and pharmacokinetics of subcutaneous meropenem as an alternative to intravenous administration

Abstract

Background: Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms.

Methods: This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50 mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8 h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were assessed.

Results: Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%-93.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8 mg/L. Simulated subcutaneous doses of 1.5 g twice daily, or 3 g continuous 24 h infusion had improved PTA relative to standard IV dosing of 1 g three times daily.

Conclusions: Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5 g twice daily or 3 g as a 24 h subcutaneous infusion could be considered for future evaluation.