Pharmacokinetic studies of anticancer drugs in tumor-bearing animals.
The pharmacokinetics of antitumor agents is a relatively recent area of research, as lack of proper specific methodology for monitoring drug levels has always hampered major efforts. Although the relationship among administered dose, tissue concentration, and therapeutic and/or toxic effects remains extremely complex, a series of experimental and clinical studies provides information on the pharmacokinetic behavior of most anticancer agents in different conditions. This review article describes examples selected from the work of this Institute on several points which may be relevant to the use of these compounds: (a) factors influencing pharmacokinetics, such as genetic constitution of the host, presence of the tumor, dose, route of administration and schedule, organ insufficiency, and interactions with other drugs; (b) drug distribution in host tissues in relation to toxic effects; (c) drug distribution to secondary tumors (metastases); (d) importance of active metabolites; and (e) drug distribution and binding to intracellular target sites. An analysis of these factors shows that many aspects are still very poorly understood and require considerable further study.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D000970:Antineoplastic Agents; D013936:Thymidine