Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy
| Autor: | Rukhsana Ahmed, Kephas Otieno, Jeanne Rini Poespoprodjo, Julie Gutman, Anne L’lanziva, Din Syafruddin, Palang Chotsiri, Puji Budi Setia Asih, Joel Tarning, Feiko O. ter Kuile, Simon Kariuki, Meghna Desai, Carole Khairallah, Ric N. Price, Peter Ouma, Vincent Were, Abraham Katana |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pediatrics
medicine.medical_specialty intermittent preventive treatment in pregnancy Population Antimalarials 03 medical and health sciences 0302 clinical medicine Dihydroartemisinin/piperaquine Pharmacokinetics Pregnancy population pharmacokinetic model Piperaquine parasitic diseases medicine qv_256 Humans Pharmacology (medical) 030212 general & internal medicine Dosing wq_200 Malaria Falciparum Artemisinin education Pharmacology 0303 health sciences education.field_of_study 030306 microbiology business.industry nonlinear mixed-effects modeling dihydroartemisinin-piperaquine medicine.disease Kenya Malaria 3. Good health wc_750 Drug Combinations Infectious Diseases Indonesia Pregnancy Complications Parasitic Quinolines Female business medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 0066-4804 |
| DOI: | 10.1128/aac.01150-20 |
| Popis: | 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. 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. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.) |
| Databáze: | OpenAIRE |
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