口服双氢青蒿素在兔和狗体内的药代动力学研究

青蒿素是一带有双氧桥结构的倍半萜内酯类抗疟药,已获我国卫生部新药审批委员会批准正式生产,用于临床。青蒿素用硼氢化钠还原得双氢青蒿素,其抗疟作用为青蒿素的4～8倍。我们曾报告给狗po青蒿素50mg/kg后,用放射免疫法在血中未测到青蒿素。

THE PHARMACOKINETICS OF DIHYDROQINGHASU GIVEN ORALLY TO RABBITS AND DOGS

Qinghaosu (QHS), also known as artemisinine and arteannuin, is isolated from the Chinese herb Artemisia annua L. It is highly active against both chloroquine-sensitive and chloroquine-resistant strains of P. berghei and has been approved by the Ministry of Health for the treatment of malaria. When QHS is treated with sodium borohydride, dihydroqinghaosu (DH QHS) is resulted with the antimalarial activity enhanced several fold. This paper reports the pharmacokinetics of DHQHS studied with the radioimmunoassay method. When the drug was given orally in tablet form to rabbits at doses of 10, 20 and 30 mg/kg, peak serum levels of 0.03, 0.05 and 0.13 micrograms/ml, respectively, were obtained in 1 to 2 h. The corresponding T1/2 of the drug were found to be 1.19, 1.00 and 1.10 h and the MRTs were 1.73, 1.36 and 1.53 h. No significant difference between dosages used was observed. When dogs were given DHQHS tablets at the dose of 20 mg/kg, a peak serum concentration of 0.13 micrograms/ml wes reached in about 2 h with a T1/2 of 2.10 h and an MRT of 3.04 h. However, when dogs were given QHS tablets at the dose of 70 mg/kg, no drug was detected in the serum. It would appear that the bioavailability of DHQHS tablets is much higher than that of QHS when given orally to the dog.