青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。

THE PHARMACOKINETICS OF A TRANSDERMAL PREPARATION OF ARTESUNATE IN MICE AND RABBITS

Qinghaosu, also known as artemisinin and arteannuin, is a new type of antimalarial drug isolated from Artemisa annua L. Its low solubility in water and oil limited its widespread clinical use. Artesunate (sodium dihydroqinghaosu hydrogen hemisuccinate monoester) is easily soluble in water and is used iv in the treatment of acute cerebral and malignant malaria. However, artesunate was shown to have a very short half-life when given iv in animals as well as in human beings. A transdermal dosage form of artesunic acid had been prepared and was reported to have reliable suppressing and killing effects on plasmobium berghei in mice. This paper reports results of pharmacokinetic studies of this preparation when applied onto a fixed area of the shaved skin of mice and rabbits. Serum concentration of the drug was determined by a method of radioimmunoassay. The drug was found to be easily absorbed from the skin. The serum concentration-time curve is depicted in figures 1. Peak concentration of 1.8 micrograms/ml was reached at about 2 h when a dose of 25 mg/kg was given to rabbits. For mice, peak serum concentrations of 2.05 and 7.11 micrograms/ml were attained in about 0.5 h after doses of 31.3 and 71.4 mg/kg, respectively, while at a dose of 6.7 mg/kg a peak level of 0.82 micrograms/ml (a concentration more than 5000 times the IC50 of artesunate in in vitro tests on plasmodium berghei for antimalarial activity) was attained at about 4 h after application of the drug. The half-lives of the drug were found to be more than 2 h for both mice and rabbits.