title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Keelan
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Saito
authors.forename: Gabrielle C
authors.initials: GC
authors.lastname: Musk
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.forename: Matthew
authors.initials: M
authors.lastname: Timmins
authors.forename: Shaofu
authors.initials: S
authors.lastname: Li
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
mesh_terms: D000650:Amnion / Q000378:metabolism*; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004917:Erythromycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism*; D007267:Injections; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D011247:Pregnancy; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017963:Azithromycin