Background:
Benzathine penicillin G (BPG) is an essential medicine to treat and prevent conditions including Group A Streptococci (GAS) infection, rheumatic heart disease and syphilis. Variability in time that penicillin concentrations remain above pharmacological correlates of protection following intramuscular (IM) injection affects therapeutic efficacy. We conducted a meta-analysis of studies reporting pharmacokinetic (PK) data on BPG to assess variability in different populations.
Methods:
Four online databases were searched for eligible studies, along with reference lists of identified reviews. Included articles reported penicillin concentration/s in humans at stated time point/s following IM BPG. Clinical, laboratory and demographic data were extracted by two reviewers and checked for consistency. The Cochrane Collaboration’s revised tool to assess risk of bias will be applied. Quantitative synthesis will use a random-effects model, with mean concentrations weighted and a one-way random effects analysis of variants comparing durations where concentrations ≥20ng/mL (conventional target for GAS).
Depending on data availability, the analysis will be repeated comparing PK variation across selected clinical and demographic features.
Preliminary findings:
Forty-one studies were included. Preliminary analysis suggests the mean plasma penicillin concentration was <20ng/mL at 21 days following 1.2MU of IM BPG. Within study samples, the highest proportion of participants >20ng/mL at 21 and 28 days was 51% and 11%, respectively.
The variability of BPG PK, together with the observation that a high proportion of people do not maintain target concentrations throughout the inter-injection period, highlights the need to reappraise target concentrations and investigate new approaches to regular BPG administration.