1. The pharmacokinetics of the antimalarial compound artemisinin were compa
red 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 fem
ale compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-f
old 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 p
lasma 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 ad
ministration, has to be taken into account in the design and interpretation
of toxicological studies of artemisinin in this species.