Skip to main content
main-content

01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

An investigation of the auto-induction of and gender-related variability in the pharmacokinetics of dihydroartemisinin in the rat

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Fanping Zhu, Fuying Du, Xinxiu Li, Jie Xing
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-379) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

FZ performed the experiments and analysed the data. FD and XL helped in performing the experiments, and FD contributed in review of manuscript. JX designed the experiments, analysed the data, and wrote the paper. All authors read and approved the final manuscript.

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 AUC0-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.
Zusatzmaterial
Authors’ original file for figure 1
12936_2012_2525_MOESM1_ESM.pdf
Authors’ original file for figure 2
12936_2012_2525_MOESM2_ESM.tiff
Authors’ original file for figure 3
12936_2012_2525_MOESM3_ESM.tiff
Authors’ original file for figure 4
12936_2012_2525_MOESM4_ESM.tiff
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2012

Malaria Journal 1/2012 Zur Ausgabe

Neu im Fachgebiet Innere Medizin


 

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise