The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers.
Southeast Asian J Trop Med Public Health
;
2004 Sep; 35(3): 575-82
Article
Dans Anglais
| IMSEAR
| ID: sea-32309
ABSTRACT
The pharmacokinetics of oral dihydroartemisinin (DHA) following the dose of 2 and 4 mg/ kg body weight dihydroartemisinin (Twisinin, T-2 Program, Thailand) and 4 mg/kg body weight oral artesunate (AS; Guilin Pharmaceutical Works, Guangxi, China) were investigated in 20 healthy Thai volunteers (10 males, 10 females). All formulations were generally well tolerated. Oral DHA was rapidly absorbed from gastrointestinal tract with marked inter-individual variation. The pharmacokinetics of DHA following the two dose levels were similar and linearity in its kinetics was observed. Based on the model-independent pharmacokinetic analysis, median (95% CI) values for Cmax of 181 (120-306) and 360 (181-658) ng/ml were achieved at 1.5 hours following 2 and 4 mg/kg body weight dose, respectively. The corresponding values for AUC0-infinity, t1/2z, CL/f and Vz/f were 377 (199-1,128) vs 907 (324-2,289) ng.h/ml, 0.96 (0.70-1.81) vs 1.2 (0.75-1.44) hours, 7.7 (4.3-12.3) vs 6.6 (3.1-10.1) l/kg, and 90.5 (28.6-178.2) vs 6.6 (3.1-10.1) ml/min/kg, respectively (2 vs 4 mg/kg dose). Oral AS was rapidly biotransformed to DHA, which was detectable in plasma as early as 15 minutes of AS dosing. Following 4 mg/kg dose, median (95% CI) value for Cmax of 519 (236-284) ng/ml was achieved at 0.7 (0.25-1.5) hours. AUC0-infinity, and t1/2z were 657 (362-2,079) ng.h/ml, 0.74 (0.34-1.42) hours, respectively. Cmax of DHA following oral AS were significantly higher, but total systemic exposure was greater following oral DHA at the same dose level (4 mg/kg body weight). There was no significant sex difference in pharmacokinetics of DHA.
Texte intégral:
Disponible
Indice:
IMSEAR (Asie du Sud-Est)
Sujet Principal:
Sesquiterpènes
/
Thaïlande
/
Femelle
/
Humains
/
Mâle
/
Biodisponibilité
/
Administration par voie orale
/
Études croisées
/
Adulte
/
Aire sous la courbe
Type d'étude:
Essai clinique contrôlé
/
Étude pronostique
Pays comme sujet:
Asie
langue:
Anglais
Texte intégral:
Southeast Asian J Trop Med Public Health
Année:
2004
Type:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS