The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children.
| Autor: | Sugiarto SR; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia., Bwire GM; Department of Clinical Pharmacy and Pharmacology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania., Moore BR; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia; Curtin Medical School, Curtin University, Bentley, Western Australia, Australia; Curtin Health Innovation Research Institute (CHIRI), Curtin University, Bentley, Western Australia, Australia., Page-Sharp M; Curtin Medical School, Curtin University, Bentley, Western Australia, Australia., Manning L; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, 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., Batty KT; Curtin Medical School, Curtin University, Bentley, Western Australia, Australia; Curtin Health Innovation Research Institute (CHIRI), Curtin University, Bentley, Western Australia, Australia., Minzi OMS; Department of Clinical Pharmacy and Pharmacology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania., Ngasala B; Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania., Davis TME; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia. Electronic address: tim.davis@uwa.edu.au., Makani J; Muhimbili Sickle Cell Centre, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania., Salman S; Medical School, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia; Clinical Pharmacology and Toxicology, PathWest, Nedlands, Western Australia, Australia. |
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| Jazyk: | angličtina |
| Zdroj: | International journal for parasitology. Drugs and drug resistance [Int J Parasitol Drugs Drug Resist] 2022 Aug; Vol. 19, pp. 31-39. Date of Electronic Publication: 2022 May 20. |
| DOI: | 10.1016/j.ijpddr.2022.05.002 |
| Abstrakt: | Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5-10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days. Sparse venous and mixed-capillary dried blood spot (DBS) samples were taken over 42 days. Plasma and DBS ARM and LUM, and their active metabolites dihydroartemisinin (DHA) and desbutyl-lumefantrine (DBL), were assayed using validated liquid chromatography-mass spectrometry. Multi-compartmental pharmacokinetic models were developed using a population approach. Plasma but not DBS concentrations of ARM/DHA were assessable. The majority (85%) of the 15 measurable values were within 95% prediction intervals from a published population pharmacokinetic ARM/DHA model in Papua New Guinean children of similar age without SCD/SCT who had uncomplicated malaria, and there was no clear sickle genotype clustering. Plasma (n = 38) and corrected DBS (n = 222) LUM concentrations were analysed using a two-compartment model. The median [inter-quartile range] LUM AUC (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Databáze: | MEDLINE |
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