Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model

Edward P. Acosta, Peta L. Grigsby, Kajal B. Larson, Amanda M. James, Mary C. Long, Lynn B. Duffy, Ken B. Waites, Miles J. Novy

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    33 Scopus citations


    Background. Our goals were to describe azithromycin (AZI) pharmacokinetics in maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) following intra-amniotic infection (IAI) with Ureaplasma in pregnant rhesus monkeys and to explore concentration-response relationships.Methods. Following intra-amniotic inoculation of Ureaplasma parvum, rhesus monkeys received AZI (12.5 mg/kg every 12 hours intravenously for 10 days; n = 10). Intensive pharmacokinetic sampling of MP, FP, and AF was scheduled following the first (ie, single) dose and the last (ie, multiple) dose. Noncompartmental and pharmacokinetic modeling methods were used.Results. The AF area under the concentration-time curve at 12 hours was 0.22 g×h/mL following a single dose and 6.3 g×h/mL at day 10. MP and AF accumulation indices were 8.4 and 19, respectively. AZI AF half-life following the single dose and multiple dose were 156 and 129 hours, respectively. The median MP:FP ratio in concomitantly drawn samples was 3.2 (range, 1.3-9.6; n = 9). Eradication of U. parvum occurred at 6.6 days, with a 95% effective concentration (EC95) of 39 ng/mL for the maximum AZI AF concentration.Conclusions. Our study demonstrates that a maternal multiple-dose AZI regimen is effective in eradicating U. parvum IAI by virtue of intra-amniotic accumulation and suggests that antenatal therapy has the potential to mitigate complications associated with U. parvum infection in pregnancy, such as preterm labor and fetal sequelae.

    Original languageEnglish (US)
    Pages (from-to)898-904
    Number of pages7
    JournalJournal of Infectious Diseases
    Issue number6
    StatePublished - Mar 2014


    • Ureaplasma
    • azithromycin
    • chorioamnionitis
    • pharmacodynamics
    • pharmacokinetics

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Infectious Diseases


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