A Strategic Approach to Positioning of Cytochrome P450 Studies and Risk Assessment for Drug-Drug Interaction in Drug Discovery

摘要

It is the mission of pharmaceutical companies to create new drugs providing excellent quality of life (QOL). This is a challenge as they need to develop drugs with potent efficacy that are also very safe. The key to the development of drugs with strong efficacy is to ensure that the exposure concentration is adequate to provide the desired effect at the expression sites after good absorption along with the suitable maintenance of the drug concentration. On the other hand, with respect to safety, it is quite the opposite. In terms of safety, it is important to develop a drug with low exposure concentrations at sites other than the effective site as well as a rapid elimination rate. For this purpose, drug metabolism and pharmacokinetics (DMPK) laboratories in pharmaceutical companies strive to develop drugs that have an appropriate metabolic fate in human subjects without inducing drug-drug interactions (DDI); this is achieved via DMPK (if toxicity is included, it is ADMET) studies using human tissues and cells in addition to the use of experimental animals.