STUDIES ON THE PHARMACOKINETICS OF QINGHAOSU AND TWO OF ITS ACTIVE DERIVATIVES IN DOGS

The pharmacokinetics of Qinghaosu and two of its active derivatives was studied by means of the RIA method developed in our laberatory. Artesunate was dissolved in a mixture of 5% NaHCO₃ and 0.9% saline and injected intravenously to 2 dogs at a dose of 6 mg/kg. The serum drug concentration-time course was found to fit a one compartment model with an elimination half-life of 0.45 h as shown in figure 1. The other pharmacokinetic parameters calculated was Cl_T=0.2 L/kg·h, Vd=0.15 L/kg.Artemether, another active derivative of Qinghaosu, was dissolved in peanut oil and given intramuscularly to dogs at doses of 10 mg/kg or 30 mg/kg. The drug was found to be easily absorbed. The serum concentration-time curve is depicted in figure 2. Peak concentrations were reached at 4.0 h after injection of 10 mg/kg and at 1.9 h after a dose of 30 mg/kg with peak serum levels of 0.7 and 3.7 μg/ml, respectively. The half-lives of the elimination phases were shown to be 4.0 h at the dose of 10 mg/kg and 6.5 h at the dose of 30 mg/kg. The data of the serum concentration time course of artemether was also treated by the statistical moment method. The MRT was found to be 7.0 h at the lower dose and 9.4 h at the higher dose.Qinghaosu was ground into very fine powder in a mortar and suspended in peanut oil. The suspension was injected intramuscularly to dogs at the dose of 10 mg/kg. Figure 3 shows that the absorption of Qinghaosu was rapid with peak level of 0.2 μg/ml at 2 h after administration. The half-life of the elimination phase was found to be 1.6 h and the MRT calculated by statistical moment method was 3.3 h.No Qinghaosu was detected by the RIA method in the serum of dogs given the drug rectally or orally.