Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom
Department of Biostatistics, University of Liverpool, Liverpool Health Partners, Liverpool, United Kingdom.
Antimicrob Agents Chemother. 2020 Aug 20;64(9). doi: 10.1128/AAC.00566-20.
An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women ( = 15 each) and lactating postpartum women ( = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis.
估计有 4000 万育龄妇女感染了三种 spp 寄生虫中的一种。通过大规模药物治疗 (MDA) 运动用吡喹酮 (PZQ) 治疗是控制流行地区人群血吸虫病的主要方法。世界卫生组织建议将孕妇和哺乳期妇女纳入血吸虫病 MDA 项目，最近的几项研究评估了 PZQ 在怀孕期间使用的安全性和疗效。迄今为止，尚无描述孕妇和哺乳期妇女 PZQ 药代动力学 (PK) 的数据。作为一项评估 PZQ 在人类妊娠期间安全性和疗效的随机对照试验的一部分，我们研究了菲律宾莱特岛感染的三种不同队列的孕妇和哺乳期妇女的 PK。具体来说，我们研究了妊娠早期和妊娠晚期的患有血吸虫病的孕妇（各 15 名）和哺乳期的产后妇女（各 15 名）的 PZQ PK 特性。我们发现，妊娠早期的妇女表观清除率增加，AUC 值降低，这可能与药物清除率的生理变化和/或口服生物利用度的变化有关。体重与表观清除率之间没有关系。血浆与母乳的平均±标准偏差分配比为 0.36±0.13。估计婴儿每天从母乳中摄入的 PZQ 剂量中位数为 0.037mg/kg 体重，明显低于抗血吸虫活性所需的剂量，且据知对婴儿无害。我们的 PK 数据不支持在服用 PZQ 后延迟 72 小时母乳喂养的建议。研究结果有助于为未来在患有血吸虫病的孕妇和哺乳期妇女中进行药物疗效研究提供信息。
