高三尖杉酯碱在大鼠及小鼠的代谢

本文报告³H-高三尖杉酯碱在正常大鼠、小鼠和荷瘤小鼠体内的吸收、分布和排泄。给大鼠静注后,t_1/2(α)和(β)分别为2.1和53.7分钟。静注后15分钟,以骨髓、肾和肝的放射性最高。荷瘤小鼠体内的放射性分布情况与正常大鼠的趋势相仿。静注后24小时,自大鼠尿排泄剂量的42.2%,在粪中排出6.3%,其中原形药放射性占剂量的15.9%。静注后48小时,自胆汁排泄剂量的57.7%,其中原形药放射性占剂量的20.2%。该碱经肌注也可被迅速吸收入血。

METABOLISM OF HOMOHARRINGTONINE IN RATS AND MICE

In the present paper, the absorption, distribution and excretion of ³H-homoharringtonine in normal rats and tumor-bearing mice are reported. After intravenous injection of ³H-homoharringtonine to normal rats, blood radioactivity level decreased rapidly with two biological phases, the distribution phase (t_1/2α=2.1 minutes) and the elimination phase (t_1/2β=53.7 minutes). The shape of the blood radioactivity level versus time curve may be fitted to a two-compartment open model. Fifteen minutes after intravenous injection of ³H-homoharringtonine to normal rats, the highest level of radioactivity was present in the bone marrow, while appreciable radioactivity was present in the kidneys, liver, lungs, spleen, heart and gastrointestinal tract. The radioactivity in the muscle, whole blood and brain was low. Two hours after injection, the radioactivity level in various tissues decreased rapidly, but that of the gastrointestinal tract decreased more slowly. Twenty-four hours after administration of ³H-homoharringtonine, only very low levels of the radioactivity were found in all tissues. In tumor-bearing mice a similar distribution pattern was observed. Twentyfour hours after intravenous injection of ³H-homoharringtonine to normal rats, the total urinary excretion of radioactivity was found to be about 42.2%, while about 6.3% was present in the feces. It was also shown that only about 15.9% of the adminstered radioactivity was excreted as unchanged homoharringtonine within 24hour period. Biliary excretion was also an important route of excretion. Normal rats excreted 57.7% of the administered radioactivity in the bile in 48 hours, while only 20.2% was in unchanged form. It was shown that homoharringtonine is distributed widely in the body and eliminated at a fairly rapid rate, thus serious accumulation in the body is unlikely.³H-homoharringtonine administered intramuscularly to normal mice was also absorbed rapidly.