Comparative Studies of the Pharmacokinetic Parameters of Dihydroartemisinin with its Disulphide Derivative.

Résumé

Malaria parasite has developed resistance to readily available and affordable drugs. Artemisinin and its derivatives are challenged by short systemic half life. The disulphide derivative of dihydroartemisinin was synthesized and confirmed of having antiplasmodial efficacy in vivo and is effective against gram negative bacteria and some fungi species in vitro. This work was aimed at assessing the pharmacokinetic parameters of the disulphide derivative of dihydroartemisinin in comparison with pure dihydroartemisinin. Sixty six rats of both sexes weighing between 180g to 220g were divided into twelve groups of five each. Therapeutic doses of dihydroartemisinin and the disulphide derivative were administered orally to each group. At interval of 1.0, 2.0, 4.0, 8.0, 12 and 24 hours, a group were sacrificed, and blood collected by cardiac puncture. The plasma obtained from the blood was spiked with benzene diazonium chloride and analyzed using UV spectrophotometer. The results obtained gave the pharmacokinetic parameters for the pure and disulphide derivative respectively as follows: AUC 9 mg.h/ml and 28.50 mg.h/ml, clearance 2.5 x 10-4 L/h/kg and 1.08 x 10-4 L/h/kg, volume of distribution 1.1 x 10-3 L/kg and 1.55 x 10-3 L/kg, elimination rate constant 0.24 h-1 and 0.070 h-1 and halflife 2.88 h and 9.9 h. The disulphide derivative with a halflife of 9.9h.,if proven clinically useful as a therapeutic agent could be used as a sustained release and dosed once daily for treatment of susceptible bacteria, fungi and malaria.