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.
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Authors | Jeffrey A Keelan, Ilias Nitsos, Masatoshi Saito, Gabrielle C Musk, Matthew W Kemp, Matthew Timmins, Shaofu Li, Nobuo Yaegashi, John P Newnham |
Journal | American journal of obstetrics and gynecology
(Am J Obstet Gynecol)
Vol. 204
Issue 6
Pg. 546.e10-7
(Jun 2011)
ISSN: 1097-6868 [Electronic] United States |
PMID | 21481833
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Mosby, Inc. All rights reserved. |
Chemical References |
- Anti-Bacterial Agents
- Erythromycin
- Azithromycin
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Topics |
- Amnion
(metabolism)
- Amniotic Fluid
(chemistry)
- Animals
- Anti-Bacterial Agents
(administration & dosage, blood, pharmacokinetics)
- Azithromycin
(administration & dosage, blood, pharmacokinetics)
- Erythromycin
(administration & dosage, blood, pharmacokinetics)
- Female
- Fetal Blood
- Fetus
(metabolism)
- Injections
- Injections, Intramuscular
- Injections, Intravenous
- Pregnancy
- Sheep
- Tissue Distribution
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