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 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.

• Authors: Edward P Acosta, Peta L Grigsby, Kajal B Larson, Amanda M James, Mary C Long, Lynn B Duffy, Ken B Waites, Miles J Novy
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 209 Issue 6 Pg. 898-904 (Mar 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24179112 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Bacterial Agents
• Azithromycin

Topics

• Administration, Intravenous
• Amniotic Fluid (metabolism, microbiology)
• Animals
• Anti-Bacterial Agents (blood, pharmacokinetics, therapeutic use)
• Azithromycin (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Chorioamnionitis (drug therapy, metabolism)
• Disease Models, Animal
• Female
• Fetal Blood (metabolism, microbiology)
• Macaca mulatta
• Pregnancy
• Pregnancy Complications, Infectious (drug therapy, metabolism)
• Ureaplasma Infections (drug therapy, metabolism)