The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin

Objective To investigate the transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. Methods Twenty-one term placentas were obtained with maternal consent immediately after delivery and a two-hour nonrecirculating perfusion of a single placental cotyledon was performed. Erythromycin (2 mu g/mL), roxithromycin (2 mu g/mL) and azithromycin (0.3 mu g/mL) were infused to the maternal inflow at a constant rate, with antipyrine as a reference compound, and their appearance in the fetal circulation was followed. Drug concentrations were measured by high performance liquid chromatography for 120 min. Results The mean transplacental transfers (TPTSS) for erythromycin, roxithromycin and azithromycin were 3.0%, 4.3% and 2.6% respectively, calculated as the ratio between the steady state concentrations in fetal venous and maternal arterial sides. Similar results were obtained when the TPT was calculated as the absolute amount of drug transferred across the placenta during 2-hour perfusion (TPTA). No significant differences were found among the three macrolides in TPTSS (P = 0.39) or TPTA (P = 0.35). The TPTSS of erythromycin, roxithromycin and azithromycin were 41%, 35% and 32% of the freely diffusable reference compound antipyrine, respectively. Steady state was reached in 60 minutes in each perfusion indicating sufficient perfusion time. Conclusion The limited transplacental transfer of erythromycin, roxithromycin and azithromycin suggests compromised efficacy in the treatment of fetal infections. On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when these three macrolides are used to treat maternal infections.