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

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

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    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
    Volume209
    Issue number6
    DOIs
    StatePublished - 2014

    Fingerprint

    Ureaplasma Infections
    Azithromycin
    Primates
    Amniotic Fluid
    Ureaplasma
    Mothers
    Pharmacokinetics
    Macaca mulatta
    Premature Obstetric Labor
    Half-Life
    Pregnancy

    Keywords

    • azithromycin
    • chorioamnionitis
    • pharmacodynamics
    • pharmacokinetics
    • Ureaplasma

    ASJC Scopus subject areas

    • Infectious Diseases
    • Immunology and Allergy

    Cite this

    Acosta, E. P., Grigsby, P., Larson, K. B., James, A. M., Long, M. C., Duffy, L. B., ... Novy, M. J. (2014). Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. Journal of Infectious Diseases, 209(6), 898-904. https://doi.org/10.1093/infdis/jit578

    Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. / Acosta, Edward P.; Grigsby, Peta; Larson, Kajal B.; James, Amanda M.; Long, Mary C.; Duffy, Lynn B.; Waites, Ken B.; Novy, Miles J.

    In: Journal of Infectious Diseases, Vol. 209, No. 6, 2014, p. 898-904.

    Research output: Contribution to journalArticle

    Acosta, EP, Grigsby, P, Larson, KB, James, AM, Long, MC, Duffy, LB, Waites, KB & Novy, MJ 2014, 'Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model', Journal of Infectious Diseases, vol. 209, no. 6, pp. 898-904. https://doi.org/10.1093/infdis/jit578
    Acosta, Edward P. ; Grigsby, Peta ; Larson, Kajal B. ; James, Amanda M. ; Long, Mary C. ; Duffy, Lynn B. ; Waites, Ken B. ; Novy, Miles J. / Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 6. pp. 898-904.
    @article{359964d8b7ba4c61b7cdac2ba1b90195,
    title = "Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model",
    abstract = "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.",
    keywords = "azithromycin, chorioamnionitis, pharmacodynamics, pharmacokinetics, Ureaplasma",
    author = "Acosta, {Edward P.} and Peta Grigsby and Larson, {Kajal B.} and James, {Amanda M.} and Long, {Mary C.} and Duffy, {Lynn B.} and Waites, {Ken B.} and Novy, {Miles J.}",
    year = "2014",
    doi = "10.1093/infdis/jit578",
    language = "English (US)",
    volume = "209",
    pages = "898--904",
    journal = "Journal of Infectious Diseases",
    issn = "0022-1899",
    publisher = "Oxford University Press",
    number = "6",

    }

    TY - JOUR

    T1 - Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model

    AU - Acosta, Edward P.

    AU - Grigsby, Peta

    AU - Larson, Kajal B.

    AU - James, Amanda M.

    AU - Long, Mary C.

    AU - Duffy, Lynn B.

    AU - Waites, Ken B.

    AU - Novy, Miles J.

    PY - 2014

    Y1 - 2014

    N2 - 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.

    AB - 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.

    KW - azithromycin

    KW - chorioamnionitis

    KW - pharmacodynamics

    KW - pharmacokinetics

    KW - Ureaplasma

    UR - http://www.scopus.com/inward/record.url?scp=84891688780&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84891688780&partnerID=8YFLogxK

    U2 - 10.1093/infdis/jit578

    DO - 10.1093/infdis/jit578

    M3 - Article

    VL - 209

    SP - 898

    EP - 904

    JO - Journal of Infectious Diseases

    JF - Journal of Infectious Diseases

    SN - 0022-1899

    IS - 6

    ER -