THE PHARMACOKINETICS AND BIOAVAILABILITY OF OMETHYLDIHYDROARTEMESININE IN THE RABBIT

The pharmacokinetics of o-methyldihydroartemisinine(MDHA, artemether) in rabbits was studied. MDHA fat emulsion was given to rabbits by intravenous infusion. Plasma C × t data were fitted to curves employing NONLIN program. The results indicated that the data fitted a two-compartment open model adequately. The pharmacokinetic parameters(mean±SD) are: t 1/2α, 0.144±0.077 h; t1/2β, 0.896±0.371 h; k₂₁, 1.235±0.705 h^-1; k₁₀, 4.143±1.370 h^-1; k₁₂, 1.140±0.951 h^-1; V₁, 0.609±0.119 L/kg; V_d(area), 2.985±0.787 L/kg; Vd_d(ss), 1.054±0.202 L/kg; Clearance, 2.401±0.339 L.kg^-1. h. MDHA oil solution was given to rabbits intramuscularly. AUC was calculated by the trapezoidal rule. Bioavailability was estimated by statistical moments. The extent of absorption was found to be 36.14±18.39%, and the absorption rate constant was 0.0377±0.0119 h^-1.