Abstract
Objective: The objective of the study was to explore the maternal-fetal pharmacokinetics of intraamniotic (IA), intravenous (IV), or intramuscular (IM) administration of erythromycin or azithromycin in a pregnant sheep model. Study Design: Pregnant ewes of 115-121 days' gestation received a single maternal IV infusion (5 mg/kg over 60 min), a single IM injection, or a single IA injection (3.2 mg/kg fetal weight) of either erythromycin lactobionate or azithromycin. Maternal/fetal blood and amniotic fluid (AF) samples were collected across 48 h for macrolide assay by liquid chromatography and tandem mass spectrometry. Results: Maternal administration achieved therapeutic maternal plasma macrolide concentrations (<0.5 μg/mL) with low concentrations in AF equivalent to less than 7% transfer; fetal plasma levels were even lower (<1.5% transfer). The IA administration achieved therapeutic concentrations in AF and sustained for 48 h, with poor maternal-fetal transfer (<1% maternal, <0.3% fetal). Modest pharmacokinetic differences were evident between erythromycin and azithromycin. Conclusion: Maternal macrolide administration achieves subtherapeutic concentrations in AF or fetal plasma, whereas a single IA injection achieves therapeutic concentrations in AF but not in maternal-fetal circulations. Combined maternal and single IA administration of macrolides may be a more effective regimen for treatment of intrauterine, but not fetal, infection.
Original language | English |
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Pages (from-to) | 546.e10-546.e17 |
Journal | American Journal of Obstetrics and Gynecology |
Volume | 204 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2011 Jun |
Keywords
- antibiotics
- intrauterine infection
- pharmacokinetics
- sheep
- ureaplasma
ASJC Scopus subject areas
- Obstetrics and Gynaecology