Pharmacodynamic-pharmacokinetic relationships and therapeutic drug monitoring. 1993

K Kobayashi, and D I Jodrell, and M J Ratain
Department of Medicine, University of Chicago, Illinois 60637.

Pharmacokinetic-pharmacodynamic studies are becoming increasingly important in the development of new anti-cancer drugs. The Hill maximal effect model describes a sigmoidal dose-response relationship and has been applied to analyses of both haematological and non-haematological toxicity. This review discusses several approaches to population pharmacodynamics, including the two stage, NONMEM, and non-parametric approaches. Pharmacodynamic models for the haematological toxicity of amonafide, carboplatin, doxorubicin, etoposide, HMBA and menogaril are discussed, as are models for non-haematological toxicity. Adaptive control methods and therapeutic drug monitoring are useful in dosing drugs with narrow therapeutic windows, but the indications for using such strategies should be carefully selected. Models for 5FU, HMBA, methotrexate, 6-mercaptopurine, carboplatin and etoposide are discussed. Limited sampling strategies can facilitate the completion of pharmacokinetic studies and should be developed during phase I testing of new compounds. A new area of future importance is the investigation of drugs with active metabolites, such as the anthracyclines and amonafide.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D001769 Blood The body fluid that circulates in the vascular system (BLOOD VESSELS). Whole blood includes PLASMA and BLOOD CELLS.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D016903 Drug Monitoring The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. Monitoring, Drug,Therapeutic Drug Monitoring,Drug Monitoring, Therapeutic,Monitoring, Therapeutic Drug

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