An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat
Abstract Background Artemisinin (QHS) and its derivatives dihydroartemisinin (DHA), artemether and artesunate have become the first-line anti-malarials in areas of multidrug resistance. Declining plasma concentrations during the repeated dosing have been reported for QHS, artemether and less convinc...
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ftdoajarticles:oai:doaj.org/article:36487a69fd394a19a83c71be230116a3 2023-05-15T15:16:08+02:00 An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat Zhu Fanping Du Fuying Li Xinxiu Xing Jie 2012-11-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-379 https://doaj.org/article/36487a69fd394a19a83c71be230116a3 EN eng BMC http://www.malariajournal.com/content/11/1/379 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-379 1475-2875 https://doaj.org/article/36487a69fd394a19a83c71be230116a3 Malaria Journal, Vol 11, Iss 1, p 379 (2012) Dihydroartemisinin Metabolites Autoinduction Sex difference Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-379 2022-12-31T01:28:54Z Abstract Background Artemisinin (QHS) and its derivatives dihydroartemisinin (DHA), artemether and artesunate have become the first-line anti-malarials in areas of multidrug resistance. Declining plasma concentrations during the repeated dosing have been reported for QHS, artemether and less convincingly for artesunate (ARS). However, there is limited information on whether the concentrations of their active metabolite DHA and its subsequent metabolites increased after multiple drug administrations. This study was designed to evaluate the potential auto-induction metabolism of DHA in animal species. The sex-specific effect on the pharmacokinetic profiles of DHA and its metabolites was studied. The pharmacokinetics of ARS, the prodrug of DHA, and its phase I/II metabolites were also investigated. Methods Two groups of rats received a single oral dose of DHA or ARS, and another two groups of rats were given oral doses of DHA or ARS once daily for five consecutive days. Plasma samples were analyzed for DHA, ARS and their phase I/II metabolites, using a validated liquid chromatography tandem mass spectrometric (LC-MS) method. Results DHA, monohydroxylated DHA (M1) and the glucuronide of DHA (DHA-G) were detected in rat plasma after oral administration of DHA or ARS. Neither DHA nor its metabolites (M1 and DHA-G) changed significantly ( P > 0.05) in AUC 0 - t after 5-day oral doses of DHA or ARS. Sex difference was observed for DHA and its metabolites (M1 and DHA-G), whereas its prodrug ARS did not show similar characteristics for the corresponding metabolites (DHA, M1 and DHA-G). Conclusions The results gave the direct evidence for the absence of auto-induction of phase I and phase II metabolism of DHA and ARS in rats. The sex effect existed for DHA but not for ARS, which could be caused by the sex-specific differences in absorption of DHA. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 379 |
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topic |
Dihydroartemisinin Metabolites Autoinduction Sex difference Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Dihydroartemisinin Metabolites Autoinduction Sex difference Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Zhu Fanping Du Fuying Li Xinxiu Xing Jie An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
topic_facet |
Dihydroartemisinin Metabolites Autoinduction Sex difference Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Artemisinin (QHS) and its derivatives dihydroartemisinin (DHA), artemether and artesunate have become the first-line anti-malarials in areas of multidrug resistance. Declining plasma concentrations during the repeated dosing have been reported for QHS, artemether and less convincingly for artesunate (ARS). However, there is limited information on whether the concentrations of their active metabolite DHA and its subsequent metabolites increased after multiple drug administrations. This study was designed to evaluate the potential auto-induction metabolism of DHA in animal species. The sex-specific effect on the pharmacokinetic profiles of DHA and its metabolites was studied. The pharmacokinetics of ARS, the prodrug of DHA, and its phase I/II metabolites were also investigated. Methods Two groups of rats received a single oral dose of DHA or ARS, and another two groups of rats were given oral doses of DHA or ARS once daily for five consecutive days. Plasma samples were analyzed for DHA, ARS and their phase I/II metabolites, using a validated liquid chromatography tandem mass spectrometric (LC-MS) method. Results DHA, monohydroxylated DHA (M1) and the glucuronide of DHA (DHA-G) were detected in rat plasma after oral administration of DHA or ARS. Neither DHA nor its metabolites (M1 and DHA-G) changed significantly ( P > 0.05) in AUC 0 - t after 5-day oral doses of DHA or ARS. Sex difference was observed for DHA and its metabolites (M1 and DHA-G), whereas its prodrug ARS did not show similar characteristics for the corresponding metabolites (DHA, M1 and DHA-G). Conclusions The results gave the direct evidence for the absence of auto-induction of phase I and phase II metabolism of DHA and ARS in rats. The sex effect existed for DHA but not for ARS, which could be caused by the sex-specific differences in absorption of DHA. |
format |
Article in Journal/Newspaper |
author |
Zhu Fanping Du Fuying Li Xinxiu Xing Jie |
author_facet |
Zhu Fanping Du Fuying Li Xinxiu Xing Jie |
author_sort |
Zhu Fanping |
title |
An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
title_short |
An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
title_full |
An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
title_fullStr |
An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
title_full_unstemmed |
An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
title_sort |
investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-379 https://doaj.org/article/36487a69fd394a19a83c71be230116a3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 379 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/379 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-379 1475-2875 https://doaj.org/article/36487a69fd394a19a83c71be230116a3 |
op_doi |
https://doi.org/10.1186/1475-2875-11-379 |
container_title |
Malaria Journal |
container_volume |
11 |
container_issue |
1 |
container_start_page |
379 |
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1766346440022425600 |