The pharmacokinetics of a single dose of artemisinin in subjects with liver cirrhosis. Bach Mai-Amsterdam Research Group on Artemisinin.
Artemisinin is mainly eliminated by hepatic transformation. To investigate whether the clearance of artemisinin in patients with liver cirrhosis is different from healthy volunteers, a pharmacokinetic study was performed in male Vietnamese patients with Child B cirrhosis of the liver who received 500 mg of artemisinin orally. The results were compared to those found in a previous study in healthy subjects. The mean (+/- SD) area under the concentration time curve was 2365 (+/- 1761) h ng/ml; the mean (+/- SD) clearance, 382 (+/- 303)L/h. The elimination half life was 4 (+/- 1.3) h extimated by log-linear regression and 2.4 +/- 0.9 h estimated by non-linear regression using a one-compartment first order elimination model. The mean (+/- SD) absorption time was 1.55 (+/- 0.8) h. These results were not different from the results of healthy subjects and show that liver disease has no effect on the availability and clearance of oral artemisinin, indicating that artemisinin has an intermediate hepatic extraction ratio and that there is no significant first pass effect.
de Vries
P J
PJ
Department of Internal Medicine, University of Amsterdam, The Netherlands.
Nguyen
X K
XK
Tran
K D
KD
Le Nguyen
B
B
Nguyen
T Y
TY
Dao
D D
DD
van Boxtel
C J
CJ
Kager
P A
PA
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics*; D037621:Artemisinins; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012717:Sesquiterpenes / Q000097:blood / Q000493:pharmacokinetics*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin