哌喹的药代动力学及其与妊娠期间歇性疟疾预防治疗结局的关系。
Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.
机构信息
Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P. O, Box 65013, Dar es Salaam, Tanzania.
Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P. O, Box 65013, Dar es Salaam, Tanzania.
出版信息
BMC Pharmacol Toxicol. 2024 Jul 8;25(1):38. doi: 10.1186/s40360-024-00762-6.
BACKGROUND
Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy.
METHODS
Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively.
RESULTS
The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004).
CONCLUSION
Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP.
TRIAL REGISTRATION
Registered 09/12/2016, PACTR201612001901313.
背景
二氢青蒿素-哌喹（DHP）在治疗妊娠期间间歇性预防治疗（IPTp）的疟疾方面比磺胺多辛-乙胺嘧啶表现出更好的效果。我们研究了第 7 天哌喹的药代动力学及其在预防怀孕期间疟疾方面的治疗效果。
方法
招募了 400 名接受每月 IPTp-DHP 的无疟疾（mRDT）孕妇，并在分娩时进行随访。每次 IPTp 后使用 UPLC/MS/MS 测定第 7 天的血浆哌喹浓度。监测 IPTp 结果（怀孕期间出现症状性疟疾和寄生虫血症、胎盘疟疾和分娩时的产妇疟疾）。使用线性混合模型和 Cox 回归分别评估第 7 天哌喹浓度和治疗结果的预测因素。
结果
每 100 人-年的风险中出现症状性疟疾和寄生虫血症的发生率分别为 2 例和 33 例。组织病理学确诊的胎盘疟疾和分娩时产妇疟疾的患病率分别为 3%和 9.8%。重复每月 IPTp-DHP 会导致第 7 天血浆哌喹浓度显著增加（p<0.001）。在接受第 1、2 和 3 次每月 IPTp-DHP 剂量后，第 7 天哌喹浓度低于治疗阈值（<30ng/mL）的女性比例分别为 6.1%、4.1%和 3.6%。母亲年龄、体重和孕期等因素不是第 7 天哌喹浓度的显著预测因素。然而，第 7 天哌喹的低血浆浓度（<30ng/mL）与怀孕期间寄生虫血症的风险增加显著相关（p=0.004）。
结论
较低的第 7 天哌喹血浆浓度是怀孕期间寄生虫血症的危险因素。单次第 7 天的血浆取样可用于监测 IPTp-DHP 期间哌喹的效果。
试验注册
于 2016 年 9 月 12 日注册，PACTR201612001901313。
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