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Pharmacokinetic Rationale for Chemotherapeutic Drugs Combined with Intra-Arterial Degradable Starch Microspheres (Spherex®)

 

作者: Carl-Johan Johansson,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 1996)
卷期: Volume 31, issue 3  

页码: 231-240

 

ISSN:0312-5963

 

年代: 1996

 

出版商: ADIS

 

数据来源: ADIS

 

摘要:

To enhance the effectiveness of regional treatment in patients with liver carcinoma, cytotoxic drugs may be combined with alternative therapeutic strategies such as partial vascular blockade using degradable starch microspheres (DSM). When DSM combined with a cytotoxic drug are infused through the hepatic artery, the steep drug concentration gradient to the tumour tissue results in higher tissue drug concentrations which may elicit an increased antitumour response. The co-injected drug should therefore possess an extensive extravascular distribution and possess a suitable dose-response relationship. Furthermore, the drug of choice should also have a high total body clearance with a large component of clearance outside the target compartment, should not interact with the spheres and should be given without inducing any back-flow. Under these assumptions, a reduced systemic exposure of a co-injected drug could be translated into an increased regional extraction ratio induced by the blood flow reduction.

 

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