Background: Syphilis in pregnancy remains a global public health concern, due to the risk of adverse birth outcomes. The World Health Organization recommends benzathine penicillin G (BPG) in pregnant women, although the optimal dosing strategy has not been clearly established, particularly in relation to the impact of gestational age. This study sought to characterize the pharmacokinetics (PK) of BPG in pregnant Ethiopian women with syphilis.
Methods: A prospective PK study was conducted among 30 pregnant women (15 in the second trimester and 15 in the third trimester) diagnosed with syphilis who received intramuscular BPG (2.4 million international units per dose) one week apart for three doses. Dried blood spot samples were collected for up to 8 weeks and benzylpenicillin concentrations quantified by liquid chromatography- mass spectrometry analysis. Population PK analysis was performed using nonlinear, mixed-effects modelling.
Results: The PK model characterized biphasic absorption with a second-phase absorption half-life of 18 days. Gestational age did not impact apparent clearance or volume of distribution of benzylpenicillin. Benzylpenicillin concentrations remained above the target threshold (18 ng/mL) for at least 28 days after the second dose in all participants (median 47 days). However, six participants (21%) exhibited subtherapeutic concentrations before their second dose on Day 7.
Conclusion: The three-dose, weekly intramuscular BPG regimen maintained therapeutic concentrations for at least four weeks, and gestational age had no impact on exposure to penicillin. Further studies of the adequacy of alternative dosage regimens in this vulnerable population are warranted.