OBJECTIVE: The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin in the term gravid woman. STUDY DESIGN: Twenty women who were scheduled for elective cesarean delivery were enrolled prospectively and received 1 g of oral azithromycin at either 6, 12, 24, 72, or 168 hours before the operation. All women received spinal anesthesia, at which time a sample of cerebrospinal fluid was obtained for analysis. Maternal serum and urine were obtained immediately before the operation. Intraoperatively, samples of myometrium, maternal adipose tissue, placenta, amniotic fluid, and umbilical arterial and venous cord blood were obtained. Azithromycin levels were determined quantitatively with high-pressure liquid chromatography with electrochemical detection. RESULTS: All participants tolerated the preoperative azithromycin without significant adverse reactions. Peak maternal serum azithromycin levels occurred within 6 hours of drug administration. Although high serum levels of azithromycin were reached early, a rapid decline in drug concentration was noted over the initial 24 hours after the drug administration (6-hour: 311 ng/mL; 24-hour: 63 ng/mL). In contrast, azithromycin levels in myometrial, adipose, and placental tissue were higher (>500 ng/mL) and sustained for up to 72 hours after administration. High urine levels of azithromycin (>5000 ng/mL) were noted similarly during the initial 72 hours after drug administration. Umbilical arterial and venous serum azithromycin levels were low (19-38 ng/mL) during the first 72 hours. Amniotic fluid levels were highest at 6 hours (151 ng/mL) and declined rapidly. Maternal cerebrospinal azithromycin concentrations were undetectable for all time points. CONCLUSION: Azithromycin has a rapid serum half-life in the term gravid woman with a prolonged half-life and high-sustained antibiotic levels noted within myometrium, adipose, and placental tissue. Given the broad antimicrobial spectrum and placental penetration, azithromycin may have potential use for the treatment of perinatal infections.