Imre Klebovich, Department of Pharmaceutics, Semmelweis University, Budapest, Hungary

The evaluation of drug–drug and drug-food interaction potential of a new chemical entity is an integral part of drug development and regulatory review before its market approval. Phase IV clinical trials and post-marketing surveillance are insufficient for detecting many drug-drug and food-drug interactions and do not alert the public to potentially dangerous interactions before a drug enters the market.
The influence of drug interactions in most cases affecting the absorption of orally administered medication. Drug-drug interactions can be classified in terms of indirect effects by one drug on gastrointestinal tract physiology influencing the absorption of other drugs, or direct interactions involving altered pH, adsorption, absorption, or chelation. Most of the drug-drug interactions result in reduced or delayed systemic drug availability.
Drug-food interactions may result in reduced, delayed, or increased systemic drug availability. The absorption of only a small number of drugs is unaffected by concomitant food intake. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter.
The degree of interaction and whether it positively or negatively affects drug absorption depends on a number of factors including the physical and chemical nature of the drug, the formulation, the type of meal, the time interval between eating and dosing and the smoking, as well.
The presentation gives an overview about the most common drug interactions referring to the recent regulatory guidelines of their examinations and tries to illustrate strategies in order to avoid them. Basic and applied industrial, academic and CRO researches play a crucial role in clarifying the different types of drug interactions and in their detailed specification, as well.
The in vitro food-drug interaction and transporter studies based on different biochemical tests, CYP isoenzyme tests and high sensitivity and selectivity HPLC-MS/MS bioanalytical methods are also of great help in the screening of interactions of previously registered drugs and new chemical entities. The pharmacovigilance reports also initiate the examination of new interactions of different types.

References
1.Percha B, Altman RB, Informatics confronts drug–drug interactions, Trends in Pharmacological Sciences, 34, 178-184, 2013

2. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf

25Oct