PRECLINICAL PHARMACOLOGICAL STUDIES OF ANTITUMOR AND ANT

抗肿瘤和ANT的临床前药理学研究

基本信息

批准号：
6352289
负责人：
KENNETH K CHAN
金额：
$ 3.1万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-12-01 至 2004-11-30
项目状态：
已结题

项目摘要

This contract provides a resource for preclinical pharmacology investigations of antitumor and anti-HIV agents under development by the Division of Cancer Treatment and Diagnosis, NCI. Defined pharmacological studies are assigned to the contractor through a Work Assignment system. These studies may include (1) development and validation of sensitive analytical methodology for quantitation of compounds in biological fluids and tissues; (2) in vitro stability and protein binding studies; (3) comparative in vitro metabolism studies using animal and human tissue preparations and expressed CYP450 isoforms; (4) determination of pharmacokinetic profiles and derived parameters following intravenous, intraperitoneal, subcutaneous (bolus and/or infusion) and oral dosing in rodents, dogs, and non-human primates; and (5) identification and pharmacokinetic analysis of drug metabolites. Data obtained in these studies are used to determine the most appropriate route, dose, and schedule of administration for achieving sustained therapeutic concentrations of an agent in biological fluids. For some compounds, particularly cytostatic antitumor or anti-HIV agents (which may be administered to patients for long periods of time), determination of oral bioavailability is emphasized. Preclinical pharmacology studies are generally performed in parallel with (and are designed to aid in the interpretation of) preclinical toxicology evaluations. Together, these investigations provide necessary data for IND filing as well as a rational basis for the clinical Phase I starting dose and dose escalation scheme.

该合同为通过癌症治疗和诊断的分配而对抗肿瘤和抗HIV剂进行临床前药理学研究提供了资源。定义的药理研究通过工作分配系统分配给承包商。这些研究可能包括（1）对敏感分析方法的开发和验证，用于定量生物液和组织中的化合物；（2）体外稳定性和蛋白质结合研究；（3）使用动物和人体组织制剂的比较体外代谢研究，并表达CYP450同工型；（4）在静脉内，腹膜内，皮下（注射和/或输注）和啮齿动物，狗和非人类灵长类动物中的药代动力学特征和衍生参数测定；（5）药物代谢产物的鉴定和药代动力学分析。在这些研究中获得的数据用于确定生物液中持续的治疗浓度的最合适的途径，剂量和给药时间表。对于某些化合物，尤其是细胞抑制剂或抗HIV剂（可以长时间给患者施用），请强调口服生物利用度。临床前药理学研究通常与临床前毒理学评估（并有助于解释）并行进行。这些研究共同提供了IND归档的必要数据，以及临床I期开始剂量和剂量升级方案的合理基础。