多烯紫杉醇的临床药物动力学。

文章的细节

引用

复制到剪贴板

克拉克SJ, Rivory LP

多烯紫杉醇的临床药物动力学。

Pharmacokinet。1999年2月,36 (2):99 - 114。doi: 10.2165 / 00003088-199936020-00002。

PubMed ID

10092957 (在PubMed

]

文摘

多烯紫杉醇(泰素帝),半合成紫杉醇类模拟(紫杉醇)是一个促进微管聚合导致细胞周期阻滞于G2 / M、细胞凋亡和细胞毒性。多烯紫杉醇具有显著的活动在乳腺癌、肺癌、卵巢癌、头部和颈部癌症。多西他赛经历了第一阶段研究的时间表,包括不同的灌注时间和各种治疗周期。研究成人剂量范围从5到145 mg / m2和那些孩子从55到235 mg / m2。最常用的方案在成人是100 mg / m2每3周。小时注入每3周一直青睐在第二和第三阶段的研究中,和多西他赛的性格等治疗后最好是三室模型描述与α,β和γ半衰期为4.5分钟,38.3分钟,12.2小时,分别。多西他赛的性格似乎是线性的,血浆浓度时间曲线下的面积(AUC)与剂量成比例地增加。多西他赛是广泛分布于组织平均体积分布的74 L / m2 100 mg / m2,之后每3周。平均后全身间隙安排大约是22 L / h / m2,主要因为肝代谢的细胞色素P450 (CYP) 3 a4系统和胆汁排泄粪便。肾排泄很小(< 5%)。 Docetaxel is > 90% bound in plasma. Population pharmacokinetic studies of docetaxel have demonstrated that clearance is significantly decreased with age, decreased body surface area, increased concentrations of alpha 1-acid glycoproteinand albumin. Importantly, patients with elevated plasma levels of bilirubin and/or transaminases have a 12 to 27% decrease in docetaxel clearance and should receive reduced doses. Although docetaxel is metabolised by CYP3A4, phase I combination studies have not shown major evidence of significant interaction between docetaxel and other drugs metabolised by the same pathway. Nevertheless, care should be taken with the use of known CYP3A4 inhibitors such as erythromycin, ketoconazole and cyclosporin. Conversely, increased doses may be required for patients receiving therapy known to induce this cytochrome (e.g. anticonvulsants). Perliminary data suggest the erythromycin breath test, an indicator of CYP3A4 function, is a predictor of toxicity after treatment with docetaxel. Such methodologies may eventually enable clinicians to individualise doses of docetaxel for patients with cancer.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
多烯紫杉醇	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节