PLASMA PHARMACOKINETICS AND TISSUE DISTRIBUTION OF PACLITAXEL IN CD2F1 MICE
PLASMA PHARMACOKINETICS AND TISSUE DISTRIBUTION OF PACLITAXEL IN CD2F1 MICE
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DOI：
10.1007/s002800050174
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发表时间：
1994-09-01
影响因子：
3
通讯作者：
EGORIN, MJ
中科院分区：
文献类型：
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作者：
EISEMAN, JL;EDDINGTON, ND;EGORIN, MJ
我们在 i 之后定义了紫杉醇的药代动力学。 v., i.p., p. o. 和 s. c.给CD2F1小鼠施用22.5mg/kg。 i后研究了另外的小鼠。 v. 11.25 mg/kg 推注给药或连续静脉注射 3 小时输注剂量为 43.24 mu g kg(-1) min(-1)。给药后5分钟至40小时内采集血浆样本。静脉注射后，对大脑、心脏、肺、肝脏、肾脏、骨骼肌和睾丸（如果适用）进行取样。剂量为22.5毫克/公斤。采用液-液萃取，然后采用等度高效液相色谱 (HPLC) 和 UV 检测来测定血浆和组织中的紫杉醇浓度。静脉注射后雄性小鼠给药后，紫杉醇清除率(CL(tb))为3.25 ml min(-1) kg(-1)，终末半衰期(t(1/2))为69 min。在我之后。 v.雌性小鼠给药，紫杉醇CL(tb)为4.54ml·min(-1)·kg(-1)，终末t(1/2)为43min。 i后紫杉醇的生物利用度类似于10%、0和0。 p.、p.o. 和 s.c.分别管理。腹腔注射后紫杉醇的生物利用度当药物以小体积递送以模拟用于评估体内抗肿瘤功效的递送方法或以大体积递送以模拟使用腹膜内注射的临床方案时，给药是相同的。局部治疗。腹腔注射后小鼠血浆中未检测到紫杉醇。在Klucel:Tween 80中以悬浮剂形式递送药物。i后药代动力学参数相似。 v.以22.5和11.25mg/kg递送紫杉醇；然而，这些研究中计算出的 CL(tb) 远低于 3 小时连续静脉注射的相关值。输液。静脉注射后给药后，紫杉醇广泛分布到除大脑和睾丸之外的所有组织。这些数据可用于解释紫杉醇的临床前疗效研究并通过缩放技术预测人体药代动力学。
We defined the pharmacokinetics of paclitaxel after i. v., i.p., p. o., and s. c. administration of 22.5 mg/kg to CD2F1 mice. Additional mice were studied after i. v. bolus dosing at 11.25 mg/kg or 3-h continuous i.v. infusions delivered at 43.24 mu g kg(-1) min(-1). Plasma was sampled between 5 min and 40 h after dosing. Brains, hearts, lungs, livers, kidneys, skeletal muscles, and, where applicable, testicles were sampled after i.v. dosing at 22.5 mg/kg. Liquid-liquid extraction followed by isocratic high-performance liquid chromatography (HPLC) with UV detection was used to determine paclitaxel concentrations in plasma and tissues. After i.v. administration to male mice, paclitaxel clearance (CL(tb)) was 3.25 ml min(-1) kg(-1) and the terminal half-life (t(1/2)) was 69 min. After i. v. administration to female mice, paclitaxel CL(tb) was 4.54 ml min(-1) kg(-1) and the terminal t(1/2) was 43 min. The bioavailability of paclitaxel was similar to 10%, 0, and 0 after i. p., p.o., and s.c. administration, respectively. Paclitaxel bioavailability after i.p. administration was the same when the drug was delivered in a small volume to mimic the delivery method used to evaluate in vivo antitumor efficacy or when it was delivered in a large volume to simulate clinical protocols using i.p. regional therapy. Paclitaxel was not detected in the plasma of mice after i.p. delivery of the drug as a sus pension in Klucel:Tween 80. Pharmacokinetic parameters were similar after i. v. delivery of paclitaxel at 22.5 and 11.25 mg/kg; however, the CL(tb) calculated in these studies was much lower than that associated with 3-h continuous i.v. infusions. After i.v. administration, paclitaxel was distributed extensively to all tissues but the brain and testicle. These data are useful in interpreting preclinical efficacy studies of paclitaxel and predicting human pharmacokinetics through scaling techniques.