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

• Published in: American journal of obstetrics and gynecology 2011-06, Vol.204 (6), p.546.e10-546.e17
• Main Authors: Keelan, Jeffrey A., PhD, Nitsos, Ilias, PhD, Saito, Masatoshi, MD, PhD, Musk, Gabrielle C., BVMS, Kemp, Matthew W., PhD, Timmins, Matthew, PhD, Li, Shaofu, BSc, Yaegashi, Nobuo, MD, PhD, Newnham, John P., MD
• Format: Article
• Language: English
• Subjects: Amnion - metabolism; Amniotic Fluid - chemistry; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; antibiotics; Azithromycin - administration & dosage; Azithromycin - blood; Azithromycin - pharmacokinetics; Erythromycin - administration & dosage; Erythromycin - blood; Erythromycin - pharmacokinetics; Female; Fetal Blood; Fetus - metabolism; Injections; Injections, Intramuscular; Injections, Intravenous; intrauterine infection; Obstetrics and Gynecology; pharmacokinetics; Pregnancy; Sheep; Tissue Distribution; ureaplasma
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2011.02.035

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 (