Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy

Chotsiri, Palang and Gutman, Julie R. and Ahmed, Rukhsana and Poespoprodjo, Jeanne Rini and Syafruddin, Din and Khairallah, Carole and Asih, Puji B.S. and L'lanziva, Anne and Otieno, Kephas and Kariuki, Simon and Ouma, Peter and Were, Vincent and Katana, Abraham and Price, Ric N. and Desai, Meghna and ter Kuile, Feiko O. and Tarning, Joel (2021) Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy. Antimicrobial Agents and Chemotherapy, 65 (3). ISSN 00664804

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Abstract

Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45 (95 confidence interval CI, 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. © 2021 Chotsiri et al.

Item Type: Article
Additional Information: Cited by: 11; All Open Access, Green Open Access, Hybrid Gold Open Access
Uncontrolled Keywords: Antimalarials; Drug Combinations; Female; Humans; Indonesia; Kenya; Malaria; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic; Quinolines; artemether plus benflumetol; clindamycin; dihydroartemisinin; dihydroartemisinin plus piperaquine; piperaquine; quinine; antimalarial agent; piperaquine; quinoline derivative; adult; Article; asymptomatic disease; blood sampling; clinical evaluation; clinical trial; concentration process; controlled study; dried blood spot testing; drug absorption; drug efficacy; female; gestational age; human; human tissue; Indonesia; Kenya; major clinical study; malaria; obstetric delivery; pharmacokinetic parameters; placenta malaria; pregnancy; pregnant woman; priority journal; second trimester pregnancy; time to treatment; treatment duration; drug combination; malaria; malaria falciparum; pregnancy; pregnancy complication
Subjects: R Medicine > RB Biomedical Sciences
Divisions: Faculty of Medicine, Public Health and Nursing > Public Health and Nutrition
Depositing User: Sri JUNANDI
Date Deposited: 24 Sep 2024 06:55
Last Modified: 24 Sep 2024 06:55
URI: https://ir.lib.ugm.ac.id/id/eprint/4730

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