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Clin Pharmacol Ther ; 102(3): 520-528, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28187497

ABSTRACT

Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed the impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected nonpregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to nonpregnant women. DHA AUC0-8hr and piperaquine AUC0-21d were 27% and 38% lower, respectively, in pregnant women receiving efavirenz compared to HIV-uninfected pregnant women. Exposure to DHA and piperaquine were lower among pregnant women and particularly in women on efavirenz, suggesting a need for dose modifications. The study of modified dosing strategies for these populations is urgently needed.


Subject(s)
Antimalarials/administration & dosage , Artemisinins/administration & dosage , Benzoxazines/administration & dosage , Malaria/prevention & control , Quinolines/administration & dosage , Adolescent , Adult , Alkynes , Antimalarials/pharmacokinetics , Area Under Curve , Artemisinins/pharmacokinetics , Chemoprevention/methods , Cyclopropanes , Dose-Response Relationship, Drug , Drug Combinations , Drug Interactions , Female , HIV Infections/drug therapy , Humans , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Parasitic/prevention & control , Quinolines/pharmacokinetics , Reverse Transcriptase Inhibitors/administration & dosage , Uganda , Young Adult
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