Pharmacokinetic parameters of artesunate and dihydroartemisinin in rats infected with Fasciola hepatica

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Serval ID
serval:BIB_E0878357BDA9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacokinetic parameters of artesunate and dihydroartemisinin in rats infected with Fasciola hepatica
Journal
Journal of Antimicrobial Chemotherapy
Author(s)
Keiser Jennifer, Gruyer Marie-Stella, Perrottet Nancy, Zanolari Boris, Mercier Thomas, Decosterd Laurent
ISSN
1460-2091
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
63
Number
3
Pages
543-549
Language
english
Notes
Comparative Study
Abstract
OBJECTIVES: The pharmacokinetic (PK) parameters of artesunate, recently discovered to possess promising trematocidal activity, and its main metabolite dihydroartemisinin (DHA) were determined in rats infected with hepatic and biliary stages of Fasciola hepatica and compared with uninfected rats after single intragastric and intravenous (iv) doses. METHODS: Rats infected with F. hepatica for 25 and 83 days and uninfected rats were cannulated in the right jugular vein and blood samples were withdrawn at selected timepoints following 10 mg/kg of iv and a single 100 mg/kg oral dose of artesunate. Plasma was analysed for artesunate and DHA by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Rats harbouring juvenile and adult F. hepatica infections revealed considerable changes in PK parameters of artesunate and DHA. Following oral administration, maximum plasma concentrations (C(max)) of artesunate and DHA were 1.8-2.3-fold higher in infected rats [artesunate: 1334 +/- 1404 ng/mL (no infection) versus 2454 +/- 1494 ng/mL (acute infection) and 2768 +/- 538 ng/mL (chronic infection); DHA: 3802 +/- 2149 ng/mL (no infection) versus 6507 +/- 3283 ng/mL (acute infection) and 9093 +/- 884 ng/mL (chronic infection)]. The AUCs of artesunate and DHA were 2.1-4.4-fold greater in infected rats. An opposite trend was observed after iv injection. C(max) and AUC of artesunate and DHA following iv dosing were 5784 +/- 3718 and 140 938 +/- 128 783 ng.min/mL and 3849 +/- 3060 and 86 107 +/- 41 863 ng.min/mL, respectively, in uninfected rats versus 2623 +/- 1554 and 21 617 +/- 12 230 ng.min/mL and 2835 +/- 980 and 64 290 +/- 29 057 ng.min/mL, respectively, in rats harbouring a chronic infection. The elimination half-lives (t(1/2)) of artesunate and DHA were considerably altered in infected rats following oral and iv administration of artesunate. CONCLUSIONS: F. hepatica infections strongly influence the disposition kinetics of artesunate and its metabolite in rats. The clinical implications of this finding need to be carefully studied.
Keywords
Animals, Anthelmintics/administration & dosage/*pharmacokinetics, Area Under Curve, Artemisinins/administration & dosage/*pharmacokinetics, Chromatography, Liquid, Fasciola hepatica/drug effects, Fascioliasis/*drug therapy/parasitology, Female, Mass Spectrometry, Plasma/*chemistry, Rats
Pubmed
Web of science
Open Access
Yes
Create date
17/02/2010 19:16
Last modification date
14/02/2022 7:57
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