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

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.

• 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)
• Copyright: Copyright © 2011 Mosby, Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Erythromycin
• Azithromycin

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