Pharmacokinetics and Safety of Levofloxacin for Treatment of Rifampicin-Resistant Tuberculosis During Pregnancy and the Postpartum Period: Results from IMPAACT P1026s.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Jennifer A Hughes, Mauricio Pinilla, Kristina M Brooks, Ahizechukwu C Eke, Alice Stek, Brookie M Best, Mark Mirochnick, Renee Browning, Lubbe Wiesner, Kathleen George, Kevin Knowles, Petra De Koker, James S Ngocho, Lee Fairlie, Nahida Chakhtoura, Anneke C Hesseling, Eric Decloedt, David E Shapiro, Marije van Schalkwyk
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引用次数: 0

Abstract

Background and objective: Treatment of rifampicin-resistant tuberculosis (RR-TB) often includes fluoroquinolones, but data on long-term exposure during and after pregnancy are limited. We examined the pharmacokinetics and safety of levofloxacin in an observational cohort of pregnant and postpartum women receiving treatment for RR-TB.

Methods: Participants were enrolled in their second or third trimester and underwent intensive pharmacokinetic sampling to quantify levofloxacin plasma concentrations at 20-26 weeks' and 30-38 weeks' gestation and at 2-8 weeks postpartum. The levofloxacin plasma concentration target was 7 µg/mL. Pharmacokinetic parameters over 12 and 24 h were described using non-compartmental analysis and within-participant comparison during pregnancy versus postpartum. Adverse events were extracted from medical records. Infants were enrolled in utero and followed on study for 4-6 months after birth.

Results: A total of 11 pregnant women, with a median age of 31 years, received RR-TB treatment including levofloxacin; 6 (55%) were living with HIV. In the second trimester, third trimester, and postpartum, median maximum plasma drug concentration values were 10.3, 10.6, and 10.6 µg/mL, and area under the concentration time curve over 12 h (AUC0-12) were 69.0, 77.6, and 80.2 µg·h/mL, respectively. Compared with postpartum, median AUCs were lower and clearance was higher in the second but not the third trimester. Eight (72%) women and seven (64%) infants experienced severe or life-threatening adverse events or outcomes that were unlikely to be related to levofloxacin.

Conclusions: Levofloxacin AUC0-12 was lower in the second trimester than the third trimester of pregnancy and the postpartum period, but exposures overall were within target ranges. Further research is warranted to explore the clinical significance of these findings.

左氧氟沙星治疗妊娠期和产后耐利福平结核病的药代动力学和安全性:IMPAACT P1026s的研究结果。
背景和目的:耐利福平结核病(RR-TB)的治疗通常包括氟喹诺酮类药物,但妊娠期间和妊娠后长期暴露的数据有限。我们在一组接受RR-TB治疗的孕妇和产后妇女中观察左氧氟沙星的药代动力学和安全性。方法:参与者在妊娠中期或晚期入组,并在妊娠20-26周和30-38周以及产后2-8周进行了密集的药代动力学采样,以量化左氧氟沙星的血浆浓度。左氧氟沙星血药浓度目标为7µg/mL。12和24小时的药代动力学参数使用非区室分析和怀孕期间与产后的参与者内比较进行描述。从医疗记录中提取不良事件。婴儿在子宫内登记,出生后随访4-6个月。结果:共有11名孕妇接受了包括左氧氟沙星在内的RR-TB治疗,中位年龄为31岁;6人(55%)携带艾滋病毒。妊娠中期、妊娠晚期和产后,血药浓度最大值中位数分别为10.3、10.6和10.6µg/mL, 12 h以上浓度时间曲线下面积(AUC0-12)分别为69.0、77.6和80.2µg·h/mL。与产后相比,中位auc较低,清除率较高的是在妊娠中期,而不是妊娠晚期。8名(72%)妇女和7名(64%)婴儿经历了不太可能与左氧氟沙星相关的严重或危及生命的不良事件或结局。结论:左氧氟沙星AUC0-12在妊娠中期低于妊娠晚期和产后,但总体暴露在目标范围内。这些发现的临床意义有待进一步研究。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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