Pharmacokinetic rationale for chemotherapeutic drugs combined with intra-arterial degradable starch microspheres (Spherex).
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.
Johansson
C J
CJ
Toxicology and Safety Assessment, Pharmacia and Upjohn AB, Helsingborg, Sweden.
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D006801:Humans; D007269:Injections, Intra-Arterial; D008102:Liver Circulation / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000628:therapy*; D008863:Microspheres; D010599:Pharmacokinetics; D013213:Starch / Q000627:therapeutic use*
D000970:Antineoplastic Agents; C044817:Spherex; D013213:Starch