Trial reportAntimicrobial agents and chemotherapy2025
Population pharmacokinetics of penicillin G: insights into increased clearance at low concentrations to guide development of improved long-acting formulations for syphilis and prevention of rheumatic fever.
Trial report in Antimicrobial agents and chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Use of Cystatin C in Tandem with Creatinine to Improve GFR Estimation and Clinical Decision Making.Journal of the American Society of Nephrology : JASN · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Although benzylpenicillin (penicillin G) is listed by the World Health Organization as an Essential Medicine, dose optimization is a persistent challenge, especially for long-acting intramuscular formulations. Maintaining sustained antibiotic exposure at target concentrations is crucial for secondary chemoprophylaxis of rheumatic heart disease and treatment of syphilis. This study compared the pharmacokinetic profile of continuous low-dose benzylpenicillin infusions with a standard-dose bolus and evaluated which renal function marker (serum creatinine, cystatin C, or combined e-glomerular filtration rate [eGFR]) best predicted clearance. Healthy adult volunteers received a single 600 mg IV benzylpenicillin bolus followed by randomization to continuous infusions targeting steady-state concentrations of 3, 6, 9, 12, or 20 ng/mL. Plasma benzylpenicillin concentrations were measured by liquid chromatography-mass spectrometry. Population pharmacokinetic analysis was performed using NONMEM by incorporating both bolus and infusion data, and various GFR estimations were evaluated as covariates for clearance. Data from 72 participants were analyzed, including 504 bolus and 389 continuous infusion samples. A two-compartment model improved fit when the ratio of central volume of distribution between bolus and low-dose infusion was incorporated, and clearance differences at steady state plasma concentration of 3 ng/mL were accounted for. Of the GFR estimations, cystatin C-based eGFR significantly enhanced model fit compared with creatinine-based equations. Benzylpenicillin pharmacokinetics at very low concentrations demonstrated both a higher volume of distribution and increased clearance. Cystatin C-based eGFR may more accurately predict benzylpenicillin clearance, enabling precision dosing for long-acting preparations used for treatment of syphilis and prevention of rheumatic fever.
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Registered trials
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