Evaluation of subcutaneous amoxicillin/clavulanic acid pharmacokinetics as an alternative to the intravenous route in older patients-the PhASAge Study

Abstract

Background: Amoxicillin/clavulanic acid (AMX/CLV) is commonly prescribed in older adults. Because oral and intravenous (IV) routes may be compromised by swallowing disorders or poor venous access, subcutaneous (SC) administration of AMX/CLV could be an alternative. The main objective of this study was to compare the bioavailability of AMX and CLV after IV and SC administration in older patients.

Patients and methods: This prospective multicentre study enrolled patients aged over 65 y receiving SC or IV AMX/CLV (1 g/0.2 g/8 h). At steady state, AMX and CLV concentrations were measured just before and after the infusion, at 2 h (in the SC group only) and at 5 h using liquid chromatography coupled to tandem mass spectrometry. Population PK analysis estimated SC AMX/CLV bioavailability in comparison to IV administration and tolerance was assessed.

Results: Seventeen patients (mean age 85.1 ± 4.8 y) were enrolled (14 in the IV group and three in the SC group). SC bioavailability of AMX and CLV was estimated at 78% and 82%, respectively. Although Cmax values were ∼45% lower with SC administration, unbound AMX concentrations remained above thresholds for common pathogens (i.e. Streptococcus pneumoniae, Enterococci and Enterobacterales) and trough concentrations were close to those observed after IV administration. On the basis of safety assessment after 122 IV and SC infusions, no serious adverse event related to the treatment occurred and local SC adverse events were transient oedema, erythema and pain.

Conclusions: The present study provides data supporting the use of SC administration of AMX/CLV in the older population.