The investigation of drug-drug and food-drug interactions and of genetic factors affecting pharmacokinetic (PK) and pharmacodynamic (PD) properties of a given drug is a fundamental instrument to improve drug safety.
Several drugs were removed from market in recent years because it became clear that they were prescribed and used in an inappropriate manner – coincidentally in combination with other common drugs or common foods –, which has caused important changes in the action of the drug. Such adverse drug interactions are of greatest concern.
To avoid fatal drug-drug, food-drug, or genotype-drug interactions the conduct of appropriate investigational studies as part of the early development plan becomes more and more essential.
Our years of experience in early-phase studies, together with our access to a large number of healthy volunteers, make us a high reliable partner for your drug-drug, food-drug, and genotype-drug interaction studies.
In case of drug-drug interactions the investigational product (molecule) affects the activity of another drug or vice versa. This may increase or decrease the effectiveness or may cause side effects of either or both drugs.
As the general population gets older and many of the elderly patients take multiple drugs, the likelihood of drug interactions increases markedly.
There are several mechanisms by which an investigational drug may interact with other drugs. For instance, important drug interactions can occur when different drugs use the same transporter (e.g., Pgp, BCRP, OATP1B1) for absorption or elimination or when they use the same enzyme for its metabolism. The most involved enzymes in drug metabolisms are members of the Cytochrome P450 family (e.g., CyP3A4, CyP1A2, CyP2C9, CyP2C19 and CyP2D6).
However, the consequence of such interactions usually is a change with regard to:
It is not necessarily the active agent, which might interact with another drug, but it could also be an attendant substance of the drug formulation.
CRS has performed more than 40 drug-drug-interaction (DDI) trials, including cocktail approaches on the basis of the Cooperstown Cocktail. More than 22 trials have been published since 1981.
Food-drug interactions might significantly affect the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a pharmaceutical product.
Although in most trials a standard high-fat American breakfast has been the interacting principle, low-fat diets, alcohol, sodium chloride and reduced alimentation have also been tested according to special requirements for a specific drug.
For food-drug interaction studies CRS collaborates with carefully selected analytical labs specialized in detailed analyses of meals and the interactions of such meals with drugs.
Genotype-drug interaction studies are required to assess potential effects of a genetic variability on pharmacokinetics (PK) and pharmacodynamics (PD) of new medications. This genetic variability might have relevance for dosing, therapeutic efficacy and the risk of side-effects.
The importance of pharmacogenetics (PG) and genotype-drug interactions has increased significantly in recent years. That’s why the U.S. Food and Drug Administration (FDA) has issued labeling regulations and posts updated pharmacogenetic information for a constantly-expanding listing of drugs.
CRS has performed a number of genotyping studies especially in healthy volunteers with CYP2D6 or CyP2C19 enzymes, who are ultra-rapid (UM), extensive (EM), intermediate (IM) or poor metabolizer.