Vigano L, Locatelli A, Grasselli G, Gianni L
Division of Medical Oncology A, Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Invest New Drugs. 2001 May;19(2):179-96. doi: 10.1023/a:1010691218625.
The taxanes' interaction with other anticancer drugs have been extensively investigated in in vitro and in animal models as well as in humans due to the outstanding antitumor activity in a broad range of malignancies. Paclitaxel and docetaxel are endowed of a rich and complex pharmacology whereby different pharmacodynamic effects are observed depending on the sequence of their administration in respect with the companion drug, and the type of drug that is combined. Pharmacokinetic interference is often but not always a basis of the pharmacodynamic effect. In addition, the vehicle of clinical formulation, especially Cremophor EL for paclitaxel, influence the pharmacological effect. Finally, new interaction based on as yet unknown mechanisms drive the two taxanes to multiple additive/synergistic relationships with new signal transduction drugs, such as modulators of the epidermal-growth-factor family of receptors and farnesyl-transferase inhibitors. The ongoing effort to better understanding such a rich pharmacology is worth continuing in view of designing new and better combinations of the taxanes.
由于紫杉烷类药物在多种恶性肿瘤中具有出色的抗肿瘤活性，其与其他抗癌药物的相互作用已在体外、动物模型以及人体中得到广泛研究。紫杉醇和多西他赛具有丰富而复杂的药理学特性，根据它们与伴随药物的给药顺序以及联合使用药物的类型，会观察到不同的药效学效应。药代动力学干扰常常（但并非总是）是药效学效应的基础。此外，临床制剂的载体，尤其是紫杉醇的聚氧乙烯蓖麻油（Cremophor EL），会影响药理作用。最后，基于尚未明确机制的新相互作用促使这两种紫杉烷类药物与新的信号转导药物，如表皮生长因子家族受体调节剂和法尼基转移酶抑制剂，形成多种相加/协同关系。鉴于设计更好的紫杉烷类药物联合方案，持续努力深入了解这种丰富的药理学特性是值得的。
