Evaluation of drug interactions and their metabolism by cytochromes P450
Almost one half of prospective drugs, including new chemical entities are not suitable for clinical use because of their metabolic unstability and for danger of drug interactions. This type of toxicity has been underlying several drug withdrawals in recent years and hence it is needed now to bring with any new compound proposed an information on its metabolism and on its interactions with major drug metabolizing enzyme systems namely with liver microsomal cytochromes P450 (CYP). Then, possibility of drug interactions with other drugs taken by the patient on the basis of drug metabolism may be evaluated to prevent significant losses in time, effort and money in drug development. The analysis of drug metabolism by individual CYPs, the possibility of drug interactions and of induction of individual CYP forms are performed with CYP in vitro systems with the respective substrates, inhibitors and inductors based on the recommendation of the U.S. Food and Drug Administration: (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ ucm093664.htm).
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