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

Objective To investigate the transplacental transfer of the macrolide antib iotics erythromycin, roxithromycin and azithromycin. Methods Twenty-one term placentas were obtained with maternal consent immed iately 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 in flow 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, roxithr omycin and azithromycin were 3.0%, 4.3% and 2.6% respectively, calculated a s the ratio between the steady state concentrations in fetal venous and mat ernal arterial sides. Similar results were obtained when the TPT was calcul ated as the absolute amount of drug transferred across the placenta during 2-hour perfusion (TPTA). No significant differences were found among the th ree macrolides in TPTSS (P = 0.39) or TPTA (P = 0.35). The TPTSS of erythro mycin, roxithromycin and azithromycin were 41%, 35% and 32% of the freely d iffusable reference compound antipyrine, respectively. Steady state was rea ched in 60 minutes in each perfusion indicating sufficient perfusion time. Conclusion The limited transplacental transfer of erythromycin, roxithromyc in 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.