Ramsey Patrick S, Vaules Megan B, Vasdev Gurinder M, Andrews William W, Ramin Kirk D
Division of Maternal-Fetal Medicine, Department of Obstetrics/Gynecology, Center for Research in Women's Health, University of Alabama at Birmingham, 35249, USA.
Am J Obstet Gynecol. 2003 Mar;188(3):714-8. doi: 10.1067/mob.2003.141.
The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin in the term gravid woman.
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.
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.
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.
本研究旨在描述足月妊娠妇女口服阿奇霉素后的药代动力学特征。
前瞻性纳入20例计划行择期剖宫产的妇女，在手术前6、12、24、72或168小时口服1克阿奇霉素。所有妇女均接受脊髓麻醉，此时采集脑脊液样本进行分析。在手术前即刻采集母体血清和尿液。术中，采集子宫肌层、母体脂肪组织、胎盘、羊水以及脐动脉和脐静脉血样本。采用高压液相色谱电化学检测法定量测定阿奇霉素水平。
所有参与者对术前阿奇霉素耐受良好，无明显不良反应。母体血清阿奇霉素水平在给药后6小时内达到峰值。尽管阿奇霉素血清水平早期较高，但在给药后的最初24小时内药物浓度迅速下降（6小时：311纳克/毫升；24小时：63纳克/毫升）。相比之下，子宫肌层、脂肪和胎盘组织中的阿奇霉素水平较高（>500纳克/毫升），给药后可持续长达72小时。在给药后的最初72小时内，尿液中阿奇霉素水平同样较高（>5000纳克/毫升）。在最初72小时内，脐动脉和脐静脉血清阿奇霉素水平较低（19 - 38纳克/毫升）。羊水水平在6小时时最高（151纳克/毫升），随后迅速下降。所有时间点母体脑脊液中均未检测到阿奇霉素浓度。
阿奇霉素在足月妊娠妇女中的血清半衰期较短，而在子宫肌层、脂肪和胎盘组织中的半衰期延长且抗生素水平持续较高。鉴于其广泛的抗菌谱和胎盘穿透性，阿奇霉素可能在围产期感染治疗中具有潜在用途。
