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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/14931
Title: Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: Absorption, bioavailability, disposition and disease effects
Authors: Rose Mcgready
Aung Pyae Phyo
Marcus J. Rijken
Joel Tarning
Niklas Lindegardh
Warunee Hanpithakpon
Hla Hla Than
Nathar Hlaing
Naw Thida Zin
Pratap Singhasivanon
Nicholas J. White
François Nosten
Shoklo Malaria Research Unit
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Mar-2012
Citation: British Journal of Clinical Pharmacology. Vol.73, No.3 (2012), 467-477
Abstract: Aim: To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance. Methods: In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4mgkg -1 ) on the first day and oral ARS (4mgkg -1 ) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4mgkg -1 day -1 ) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum). Results: I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n= 20) and in controls (n= 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ngml -1 h)/(mgkg -1 )] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P= 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P= 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P= 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P= 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P= 0.084). Conclusions: This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84857003505&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/14931
ISSN: 13652125
03065251
Appears in Collections:Scopus 2011-2015

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