Preclinical pharmacology of the natural marine product dolastatin 10 (NSC 376128).
Preclinical pharmacology of the natural marine product dolastatin 10 (NSC 376128).
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发表时间：
1994-05
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通讯作者：
R. Newman;A. Fuentes;J. Covey;J. Benvenuto
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作者：
R. Newman;A. Fuentes;J. Covey;J. Benvenuto
对天然海产品多拉司他汀10进行临床前药理学和药代动力学研究。在静脉内、皮下和腹膜内给药途径后，在 CD2F1 小鼠中测定了 [3H]多拉司他汀 10 的药代动力学。静脉注射（0.24mg/kg）后，血浆药物浓度迅速下降并从血浆中清除，半衰期为5.6小时。皮下注射 0.32 mg/kg 剂量后，多拉司他汀 10 浓度缓慢升至最高 11 ng/ml，然后下降，消除半衰期为 3.7 小时。发现血浆中的大部分放射性来自药物衍生的放射性标记产品，而不是来自母体化合物。在人、狗和小鼠血浆中多拉司他汀10的尿排泄率为81%。与全肝匀浆或来自肝脏的 S9 级分一起孵育后，多拉司他汀 10 快速转化为极性更强的产物。通过质谱分析，其中一种代谢物被鉴定为多拉司他汀 10 的二羟基衍生物。
The preclinical pharmacology and pharmacokinetics of the natural marine product dolastatin 10 were investigated. Pharmacokinetics of [3H]dolastatin 10 were determined in CD2F1 mice after intravenous, subcutaneous, and intraperitoneal routes of administration. After intravenous injection (0.24 mg/kg), plasma drug concentration declined rapidly and was cleared from plasma with a half-life of 5.6 hr. After a subcutaneous dose of 0.32 mg/kg, dolastatin 10 concentrations slowly rose to a maximum of 11 ng/ml and then declined with an elimination half-life of 3.7 hr. Most of the radioactivity in plasma was found to be from drug-derived radiolabeled products and not from parent compound. Urinary excretion of dolastatin 10 was 81%) in human, dog, and mouse plasmas. Dolastatin 10 underwent rapid conversion to more polar products after incubation with whole liver homogenate or the S9 fraction from rate liver. One of these metabolites was identified by mass spectrometry as a dihydroxy derivative of dolastatin 10.