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The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin
Author(s) -
Heikkinen Tuija,
Laine Kari,
Neuvonen Pertti J.,
Ekblad Ulla
Publication year - 2000
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/j.1471-0528.2000.tb13339.x
Subject(s) - roxithromycin , transplacental , azithromycin , erythromycin , antibiotics , placenta , perfusion , fetal circulation , fetus , antibacterial agent , pharmacology , chemistry , medicine , pregnancy , biology , biochemistry , genetics
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 μg/mL), roxithromycin (2 μg/mL) and azithromycin (0.3 μg/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 (TPT ss ) 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 (TPT A ). No significant differences were found among the three macrolides in TPT SS ( P = 0.39 ) or TPT A ( P = 0.35 ). The TPT SS 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.