Maternal-amniotic-fetal distribution of macrolide antibiotics following intravenous, intramuscular, and intraamniotic administration in late pregnant sheep

Jeffrey A. Keelan, Ilias Nitsos, Masatoshi Saito, Gabrielle C. Musk, Matthew W. Kemp, Matthew Timmins, Shaofu Li, Nobuo Yaegashi, John P. Newnham

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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 languageEnglish
Pages (from-to)546.e10-546.e17
JournalAmerican Journal of Obstetrics and Gynecology
Volume204
Issue number6
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • antibiotics
  • intrauterine infection
  • pharmacokinetics
  • sheep
  • ureaplasma

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

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