مورد إلكتروني
Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine.
| العنوان: | Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine. |
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| المؤلفون: | Savic, Rada M |
| المصدر: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America; vol 67, iss 7, 1079-1088; 1058-4838 |
| بيانات النشر: | eScholarship, University of California 2018-09-01 |
| تفاصيل مُضافة: | Savic, Rada M Jagannathan, Prasanna Kajubi, Richard Huang, Liusheng Zhang, Nan Were, Moses Kakuru, Abel Muhindo, Mary K Mwebaza, Norah Wallender, Erika Clark, Tamara D Opira, Bishop Kamya, Moses Havlir, Diane V Rosenthal, Philip J Dorsey, Grant Aweeka, Francesca T |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | BackgroundDihydroartemisinin-piperaquine (DHA-PQ) is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine (PQ) exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies.MethodsHuman immunodeficiency virus-uninfected pregnant women (n = 300) were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks' gestation and randomized to sulfadoxine-pyrimethamine every 8 weeks, DHA-PQ every 8 weeks, or DHA-PQ every 4 weeks during pregnancy. Pharmacokinetic sampling for PQ was performed every 4 weeks, and an intensive pharmacokinetic substudy was performed in 30 women at 28 weeks' gestation. Concentration-effect relationships were assessed between exposure to PQ; the prevalence of Plasmodium falciparum infection during pregnancy; outcomes at delivery including placental malaria, low birth weight, and preterm birth; and risks for toxicity. Simulations of new dosing scenarios were performed.ResultsModel-defined PQ target venous plasma concentrations of 13.9 ng/mL provided 99% protection from P. falciparum infection during pregnancy. Each 10-day increase in time above target PQ concentrations was associated with reduced odds of placental parasitemia, preterm birth, and low birth weight, though increases in PQ concentrations were associated with QT interval prolongation. Modeling suggests that daily or weekly administration of lower dosages of PQ, compared to standard dosing, will maintain PQ trough levels above target concentrations with reduced PQ peak levels, potentially limiting toxicity.ConclusionsThe protective efficacy of IPTp with DHA-PQ was strongly associated with higher drug exposure. Studies of the efficacy and safety of alternative DHA-PQ IPTp dosing strategies are warranted.Clinical trials registrationNCT02163447. |
| مصطلحات الفهرس: | Humans, Pregnancy Complications, Parasitic, Malaria, Falciparum, Artemisinins, Quinolines, Drug Combinations, Pregnancy Outcome, Drug Administration Schedule, Double-Blind Method, Pregnancy, Models, Biological, Infant, Newborn, Female, Prevention, Rare Diseases, Clinical Trials and Supportive Activities, Pediatric, Perinatal Period - Conditions Originating in Perinatal Period, Preterm, Low Birth Weight and Health of the Newborn, Clinical Research, Infant Mortality, Vector-Borne Diseases, Infectious Diseases, 6.1 Pharmaceuticals, Prevention of disease and conditions, and promotion of well-being, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, 3.3 Nutrition and chemoprevention, 5.1 Pharmaceuticals, Infection, Reproductive health and childbirth, Good Health and Well Being, intermittent preventive treatment for malaria in pregnancy, dihydroartemisinin-piperaquine, Plasmodium falciparum, pharmacokinetic/pharmacodynamic modeling, Biological Sciences, Medical and Health Sciences, Microbiology, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol 67, iss 7, 1079-1088 1058-4838 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt1cf810jr qt1cf810jr https://escholarship.org/uc/item/1cf810jrTest https://escholarship.orgTest/ 1391610820 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1391610820 |
| قاعدة البيانات: | OAIster |
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