Pharmacokinetics of Artesunate following Oral and Rectal Administration in Healthy Sudanese Volunteers

Abstract

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross- over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection.

Pharmacokinetic parameters were derived from the main metabolite α-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma.

Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC₀-∞ (P<0.05 95% confidence interval (Cl) −1168.73, −667.61 ng.h/mL⁻¹) and C_max(P<0.05;95%Cl −419.73, −171.44 ng/mL_{− 1}, and had shorter t_max (P<0.05; 95% Cl −0.97, −0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination halflife between both routes of administration (P> 0.05; 95% Cl −0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation%)54.9(24.8%)%]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.