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Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
1999 (English)In: Xenobiotica, ISSN 0049-8254, E-ISSN 1366-5928, Vol. 29, no 2, 195-204 p.Article in journal (Refereed) Published
Abstract [en]

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg(-1)) or i.p. (50 mg.kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95 % confidence interval: 10.4, 13.0) l.h(-1).kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) I.h(-1).kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was similar to 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8+/-2.0%) compared with the female rat (11.7+/-2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.

Place, publisher, year, edition, pages
1999. Vol. 29, no 2, 195-204 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-208922DOI: 10.1080/004982599238740ISI: 000078963600005OAI: oai:DiVA.org:uu-208922DiVA: diva2:655505
Available from: 2013-10-11 Created: 2013-10-11 Last updated: 2017-12-06Bibliographically approved

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Svensson, Ulrika S H

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