Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy.

Chotsiri, Palang, Gutman, Julie, Ahmed, Rukhsana, Poespoprodjo, Jeanne Rini, Syafruddin, Din, Khairallah, Carole, Asih, Puji B S, L'lanziva, Anne, Otieno, Kephas, Kariuki, Simon, Ouma, Peter, Were, Vincent, Katana, Abraham, Price, Ric N, Desai, Meghna, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 and Tarning, Joel (2021) 'Piperaquine pharmacokinetics during intermittent preventive treatment for malaria in pregnancy.'. Antimicrobial Agents and Chemotherapy, Vol 65, Issue 3, e01150-20.

Text STOPMIP_PopPK_MS_R2.0_clean_version.docx - Accepted Version Available under License Creative Commons Attribution. Download (1MB)

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 4-8 weeks intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modelling with a prior approach. In total data from 366 Kenyan and 101 Indonesian women were analysed. 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% CI: 1.8-26.5) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/mL). Translational simulations suggest that providing the full treatment dose of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of a DP has the potential to offer optimal prevention of malaria during pregnancy.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WQ Obstetrics > Pregnancy > WQ 200 General works
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1128/AAC.01150-20
Depositing User:	Tracy Seddon
Date Deposited:	06 Jan 2021 11:13
Last Modified:	12 Apr 2021 09:56
URI:	https://archive.lstmed.ac.uk/id/eprint/16585

Statistics

View details

Actions (login required)

Edit Item