Pharmacokinetics artemisinins

Svensson, U.S., Alin, H., Karlsson, M.O., Bergqvist, Y., and Ashton, M., Population pharmacokinetic and pharmacodjmamic modeling of artemisinin and mefloquine enantiomers in patients with falciparum malaria, Eur.. Clin. Pharmacol, 58, 339-351, 2002. 

Hassan Alin M, Ashton M, Kihamia CM, Mtey GJ, Bjorkman A. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesu-nate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996 90(l) 61-5. 

J. S. Sidhu, M. Ashton, N. V. Huong, et al.. Artemisinin population pharmacokinetics in children and adults with uncomplicated falciparum malaria. Br I Clin Pharmacol 45 347-354 (1998). 

A characteristic of artemisinin and its related endoperoxide drugs is the rapid clearance of parasites in the blood in almost 48 horns. Titulaer obtained pharmacokinetic data for the oral, intramuscular and rectal administration of artemisinin to volunteers [132], Rapid but incomplete absorption of artemisinin given orally occurs in humans with a mean absorption time of... 

Artemether pretreatment appears to modestly reduce mefloquine levels, whereas artemisinin and dihydroartemisinin do not affect the pharmacokinetics of mefloquine. If mefloquine is given shortly after artesunate its levels are lowered, but giving mefloquine two days in to artesunate treatment appears to raise mefloquine levels. The combined use of mefloquine with artemisinin derivatives might improve antimalarial activity. See also Co-artemeth-er + Mefloquine , p.224... 

It is worth noting that the two optical isomers of ferroquine exist due to the planar chirality of the unsymmetrically 1,2-substituted ferrocene moiety. Both enantiomers were prepared by enzymatic resolution of an ester intermediate in >98% optical purity. Both isomers display similar activity in vitro " Although both enantiomers are less active than the racemate in vivo the (+)-enantiomer displays better curative effects than the optical antipode. This different behavior indicates different pharmacokinetics of the two enantiomers. Ferrocene derivatives of other antimalarial drugs like artemisinine, quinine, and mefloquine have also been tested, as well as various other chloroquine-derived organometallics. Moss and coworkers synthesized and tested chloroquine and ferroquine derivatives with other organometallic groups. 

Li, L., Pabbisetty, D., Carvalho, R,Avery, M.A.,Wilhamson, J., Avery, B.A. (2008) Ultra-performance liqnid chromatography-tandem mass spectrometric method for the determination of Artemisinin in rat semm and its apphcation in pharmacokinetics. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences, 867,131—137. 

German PI, Aweeka FT. Clinical pharmacology of artemisinin-based combination therapies. Clin Pharmacokinet 2008 47(2) 91-102. 

Synthetic trioxanes, simplified analogs of artemisinin, supposed to act in the same way, have also been developed (37). Future studies will provide information on die pharmacokinetics parameters of these artemisinin mimicks and tell us if these molecules have longer half-life times in plasma. 

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