Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 126

There is a lot of potential for drugs to interact with other drugs or dietary factors. A lot of the potential for interaction occurs through the effect of drugs on enzymes in the liver, both induction and inhibition. A lot of these interactions can now be predicted from in vitro studies but if such studies suggest a clinically relevant interaction may exist, many regulatory authorities will require that the effect be quantified more accurately via a clinical interaction study. An example of this is when there are concerns that a drug may cause an interaction mediated through an effect on cytochrome P450 3A4. Midazolam is almost exclusively metabolised by this enzyme. If a drug in development is thought to interact through an effect on cytochrome P450 3A4, then dosing the drug with and without midazolam will allow you to quantify the effect. If the drug is an enzyme inducer, then the amount of midazolam measured in the plasma will be less and if an enzyme inhibitor, the amount of midazolam measured in the plasma will be greater.