Drug interaction studies during drug development: which, when, how?
Drug-drug interaction studies have become an important aspect of the development process of new drugs. Since formal studies of all possible interactions are neither practicable nor suggestive, a careful selection of a limited number of drug combinations to be investigated during the development phase is indicated. Priorities should be based on the likelihood of certain combinations to occur in clinical practice as well as on risks associated with them. In the main, clinical drug interaction studies are performed during late phase II and phase III of clinical drug development. In some exceptional cases clinical interaction studies are necessary at an earlier stage of development. This counts especially for drugs with a small therapeutic range and a steep course of the dose-response curve and especially for drug interactions which may effect vital processes. For all other drugs often administered together an initial screen for pharmacokinetic and/or pharmacodynamic interactions with plasma level measurements and examinations of a possible concentration-effect relationship might be sufficient. Taking these criteria into account an interaction program for new drugs under development with different indications like cardiovascular diseases, respiratory diseases, diseases of the central nervous system as well as rheumatic diseases, metabolic diseases and infectious diseases was developed.
Kuhlmann
J
J
Bayer AG, Pharma Research and Development, Medicine and Development, Institute for Clinical Pharmacology International, Wuppertal, Germany.
D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D010599:Pharmacokinetics