Piperaquine Pharmacokinetic and Pharmacodynamic Profiles in Healthy Volunteers of Papua New Guinea after Administration of Three-Monthly Doses of Dihydroartemisinin-Piperaquine.

Autor: Millat-Martínez P; ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain., Salman S; Medical School, The University of Western Australiagrid.1012.2, Crawley, Perth, Western Australia, Australia.; Clinical Pharmacology and Toxicology, PathWest, Nedlands, Western Australia, Australia.; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia., Moore BR; Medical School, The University of Western Australiagrid.1012.2, Crawley, Perth, Western Australia, Australia.; Curtin Medical School, Curtin Universitygrid.1032.0, Bentley, Perth, Western Australia, Australia.; Curtin Health Innovation Research Institute, Curtin Universitygrid.1032.0, Bentley, Perth, Western Australia, Australia., Baro B; ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain., Page-Sharp M; Curtin Medical School, Curtin Universitygrid.1032.0, Bentley, Perth, Western Australia, Australia., Batty KT; Curtin Medical School, Curtin Universitygrid.1032.0, Bentley, Perth, Western Australia, Australia.; Curtin Health Innovation Research Institute, Curtin Universitygrid.1032.0, Bentley, Perth, Western Australia, Australia., Robinson LJ; Vector-borne Diseases Unit, Papua New Guinea Institute of Medical Researchgrid.417153.5, Madang, Papua New Guinea.; Burnet Institute, Melbourne, Victoria, Australia.; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia., Pomat W; Vector-borne Diseases Unit, Papua New Guinea Institute of Medical Researchgrid.417153.5, Madang, Papua New Guinea., Karunajeewa H; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medicine-Western Health, The University of Melbourne, Melbourne, Victoria, Australia., Laman M; Vector-borne Diseases Unit, Papua New Guinea Institute of Medical Researchgrid.417153.5, Madang, Papua New Guinea., Manning L; Medical School, The University of Western Australiagrid.1012.2, Crawley, Perth, Western Australia, Australia.; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.; Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, Australia., Mitjà O; Fight AIDS and Infectious Diseases Foundation, Badalona, Spain.; Infectious Disease Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.; Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.; Lihir Medical Centre, International SOS, Lihir Island, Papua New Guinea., Bassat Q; ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.; ICREA, Pg. Lluís Companys 23, Barcelona, Spain.; Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Barcelona, Spain.; Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2022 Aug 16; Vol. 66 (8), pp. e0018522. Date of Electronic Publication: 2022 Jul 06.
DOI: 10.1128/aac.00185-22
Abstrakt: Mass drug administration (MDA) with monthly dihydroartemisinin-piperaquine (DHA-PQP) appears useful in malaria control and elimination strategies. Determining the relationship between consecutive piperaquine phosphate (PQP) exposure and its impact on QT interval prolongation is a key safety consideration for MDA campaigns. Healthy volunteers from Papua New Guinea received a 3-day course of DHA-PQP (2.1/17.1 mg/kg) monthly for 3 consecutive months in a single arm longitudinal study. Plasma PQP concentrations were measured after the third dose of each course (at 52-54 h) and at 0 h of course 3. Twelve-lead electrocardiographic readings were conducted at 0 h, 48 h, 52 h, and day 7 of each course. QT interval corrected by Fridericia's formula (QTcF) was measured at each time point. A pharmacokinetic-pharmacodynamic model using nonlinear mixed effects models was developed to correlate PQP concentrations with QTcF. Ten thousand female and 10,000 male individuals were simulated at each treatment course. Eighty-two participants were included; mean age was 28.3 years (standard deviation [SD] ±12.3 years), and 36 (44%) were female. Pharmacokinetic-pharmacodynamic models were determined with 290 PQP concentrations and 868 QTcF observations. The average baseline QTcF was 392 ms with a between-subject variability SD ±14.4 ms and between-occasion variability SD ±3.64 ms. From the population modeled, only 0.08% of males and 0.45% of females would be at risk of an absolute QTcF of >500 ms. DHA-PQP is safe at standard doses in consecutive months, and the likelihood of severe cardiac events occurring during an MDA campaign is very low. This study has been registered at ClinicalTrials.gov under identifier NCT02605720.
Databáze: MEDLINE