Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy
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 adjus...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2021
|
| _version_ | 1797066525873537024 |
|---|---|
| author | Chotsiri, P Gutman, J Ahmed, R Poespoprodjo, JR Syafruddin, D Khairallah, C Asih, PBS L'lanziva, A Otieno, K Kariuki, S Ouma, P Were, V Katana, A Price, RN Desai, M Ter Kuile, FO Tarning, J |
| author_facet | Chotsiri, P Gutman, J Ahmed, R Poespoprodjo, JR Syafruddin, D Khairallah, C Asih, PBS L'lanziva, A Otieno, K Kariuki, S Ouma, P Were, V Katana, A Price, RN Desai, M Ter Kuile, FO Tarning, J |
| author_sort | Chotsiri, P |
| collection | OXFORD |
| description | 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.) |
| first_indexed | 2024-03-06T21:43:19Z |
| format | Journal article |
| id | oxford-uuid:48afc2f7-20a0-403a-bfbd-aeb4fc8200fc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:43:19Z |
| publishDate | 2021 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:48afc2f7-20a0-403a-bfbd-aeb4fc8200fc2022-03-26T15:27:16ZPiperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:48afc2f7-20a0-403a-bfbd-aeb4fc8200fcEnglishSymplectic ElementsAmerican Society for Microbiology2021Chotsiri, PGutman, JAhmed, RPoespoprodjo, JRSyafruddin, DKhairallah, CAsih, PBSL'lanziva, AOtieno, KKariuki, SOuma, PWere, VKatana, APrice, RNDesai, MTer Kuile, FOTarning, JDihydroartemisinin-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.) |
| spellingShingle | Chotsiri, P Gutman, J Ahmed, R Poespoprodjo, JR Syafruddin, D Khairallah, C Asih, PBS L'lanziva, A Otieno, K Kariuki, S Ouma, P Were, V Katana, A Price, RN Desai, M Ter Kuile, FO Tarning, J Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title | Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title_full | Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title_fullStr | Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title_full_unstemmed | Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title_short | Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| title_sort | piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy |
| work_keys_str_mv | AT chotsirip piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT gutmanj piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT ahmedr piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT poespoprodjojr piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT syafruddind piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT khairallahc piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT asihpbs piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT llanzivaa piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT otienok piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT kariukis piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT oumap piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT werev piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT katanaa piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT pricern piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT desaim piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT terkuilefo piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy AT tarningj piperaquinepharmacokineticsduringintermittentpreventivetreatmentformalariainpregnancy |