Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers

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 alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P < 0.05 95% confidence interval (CI) - 1168.73, - 667.61 ng.h/mL(-1)) and C-max (P < 0.05; 95% CI -419.73, -171.44 ng/mL(-1)) and had shorter t(max), (P < 0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life 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.