Keywords:
Acute rheumatic fever; BPG; Penicillin; Rheumatic heart disease; Subcutaneous injection
Abstract:
Objectives
This Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10 weekly subcutaneous injections of penicillin (SCIP) in young people with a history of acute rheumatic fever (ARF).
Methods
Participants received 7.2–10.8 MU (13.8–20.7 mL) of Bicillin-LA® via subcutaneous injection in Wellington, New Zealand. A subset underwent intensive safety monitoring and serial dried blood spot collection for penicillin assay. Penicillin concentrations informed a population pharmacokinetic model based on 169 data points from 31 participants. The proportion of time penicillin concentrations remained above a range of plausible pharmacological correlates of protection was estimated for SCIP and compared with estimates for intramuscular benzathine penicillin G (BPG).
Results
Fifty-five participants received SCIP at least once, totalling 182 doses. No recurrent ARF or breakthrough streptococcal throat infections were reported. Model-based simulations indicated that SCIP outperformed intramuscular BPG in maintaining protective concentrations across nearly all plausible pharmacological target correlates of protection (10–20 ng/mL). SCIP performed even more favourably when considering modified weight-based dosing or missed BPG injections.
Conclusions
SCIP is safe, well tolerated and demonstrates favourable penicillin exposure for most individuals. Future research should explore the effectiveness of SCIP over longer periods and in diverse populations and settings.