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 µg×h/mL following a single dose and 6.3 µg×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: Ureaplasma; azithromycin; chorioamnionitis; pharmacodynamics; pharmacokinetics.