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

J.A. Keelan; I. Nitsos; M. Saito; G.C. Musk; M.W. Kemp; M. Timmins; S. Li; N. Yaegashi; J.P. Newnham

doi:10.1016/j.ajog.2011.02.035

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

Journal article

Peer reviewed

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

J.A. Keelan, I. Nitsos, M. Saito, G.C. Musk, M.W. Kemp, M. Timmins, S. Li, N. Yaegashi and J.P. Newnham

American Journal of Obstetrics and Gynecology, Vol.204(6), pp.546.e10-546.e17

2011

DOI: https://doi.org/10.1016/j.ajog.2011.02.035

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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.

Details

Title: Maternal-amniotic-fetal distribution of macrolide antibiotics following intravenous, intramuscular, and intraamniotic administration in late pregnant sheep
Authors/Creators: J.A. Keelan (Author/Creator) - The University of Western Australia
I. Nitsos (Author/Creator) - The University of Western Australia
M. Saito (Author/Creator) - Tohoku University Hospital
G.C. Musk (Author/Creator) - The University of Western Australia
M.W. Kemp (Author/Creator) - The University of Western Australia
M. Timmins (Author/Creator) - The University of Western Australia
S. Li (Author/Creator) - The University of Western Australia
N. Yaegashi (Author/Creator) - Tohoku University Hospital
J.P. Newnham (Author/Creator) - The University of Western Australia
Publication Details: American Journal of Obstetrics and Gynecology, Vol.204(6), pp.546.e10-546.e17
Publisher: Mosby Inc
Identifiers: 991005540910407891
Copyright: © 2011 Mosby, Inc.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.72 Obstetrics & Gynecology; 1.72.924 Preterm Birth Causes
Web Of Science research areas: Obstetrics & Gynecology
ESI research areas: Clinical Medicine