双氢青蒿素在人的药代动力学及与青蒿素的比较  

PHARMACOKINETICS OF DIHYDROQINGHAOSU IN HUMAN VOLUNTEERS AND COMPARISON WITH QINGHAOSU

作　　者：赵凯存[1] 宋振玉[1] 

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《药学学报》1993年第5期342-346,共5页Acta Pharmaceutica Sinica

摘　　要：用放射免疫测定法研究青蒿素和双氢青蒿素在人的药代动力学结果:人口服青蒿素片剂15 mg/kg后1.5 h,血药峰值达0.09μg/ml,MRT为3.27 h,而口服双氢青蒿素仅1.1 mg/kg和2.2mg/kg后1.33 h,血药峰浓度分别为0.13μg/ml和0.71μg/ml,MRT分别为2.36和2.26 h,可见,青蒿素片剂的生物利用度仅为双氢青蒿素的1.62%～10.08%,所以口服宜用双氢青蒿素。直肠给青蒿素栓剂15 mg/kg和双氢青蒿素栓剂8 mg/kg后,血药分别于4.6 h和4.7 h达峰浓度0.04 μg/ml和0.11 μg/ml,MRT分别为6.98 h和6.96 h,可见青蒿素栓剂的生物利用度仅为双氢青蒿素者的29%,作为栓剂也可用双氢青蒿素。Qinghaosu (QHS), also known as artemisinin and arteannuin, is a novel type of sesquiterpene with a peroxide linkage isolated from the Chinese hero Artemisia annua L. Since its discovery as an antimalarial with low toxicity, hundreds of derivatives have been synthesized among them artesunate (ATS), artemether (ATM) and dihydroqinghaosu (DHQHS) were found to be more active than QHS itself. A suppository of QHS, a dual-pack dosage form of ATS (artesunic acid to be dissolved in sodium bicarbonate solution just before iv injection) and an oil solution of ATM for im injection had been approved by our Ministry of Health for clinical use. However, a preparation for oral administration is still not available. We have reported that when dogs were given QHS tablets orally at the dose of 70 mg/kg, no drug was detected in the serum using the RIA method, whereas appreciable serum concentration was found by the same method when dogs were given DHQHS tablets at a dose as low as 10 mg/kg. This paper reports the pharmacokinetics of DHQHS in man studied with the RIA method and compared with QHS. When DHQHS in tablet form was given to human volunteers at doses of 1.1～2.2 mg/kg, peak serum levels of 0.13～0.71 μg/ml were obtained in 1.33 h with MRT of 2.26～2.36 h. When QHS tablets were given at the dose as high as 15 mg/kg, however, the peak serum level found in 1.5 h was only 0.09 μg/ml with MRT of 1.33 h. Therefore, the bioavailability of QHS tablets is only 1.62～10.08% that of DHQHS. It would, therefore, be warrantable to use DHQHS tablets orally but not QHS tablets. When suppositories of DHQHS and QHS at doses of 8 and 15 mg/kg, respectively, were given rectally to man, peak serum drug levels of 0.11 and 0.04 μg/ml were reached in 4.7 and 4.6 h ( with MRT of 6.96 and 6.98 h) respectively. Apparently, the bioavailability of QHS suppository is only about 29% that of DHQHS suppository. It would appear, therefore, that for making suppositories DHQHS may also be used.

关 键 词：青蒿素 双氢青蒿素 药代动力学 

分 类 号：R969.1[医药卫生—药理学]