Drug-drug interactions can have a significant impact on drug efficacy and patient safety. As such, regulators have made the prediction of drug-drug interactions a requisite in the development of new drug candidates, which has to be supplied as part of the submission of the registration dossier. In vitro identification and measurement of the contribution of major cytochrome P450 enzymes involved in human metabolism of a new drug candidate (CYP phenotyping), helps predict the impact of co-administered drugs on the pharmacokinetics of the new chemical entity.
Traditionally, these studies were conducted using one of three approaches – correlation analysis, antibody or chemical inhibition, and metabolism by recombinant human enzymes. However, each of these approaches has advantages and disadvantages, which is why a combination is recommended by the FDA and EMA to reliably identify the CYPs involved in the metabolism of a compound. For example, correlation analysis doesn’t provide any quantitative measurement of the contribution of each CYP to the metabolism of a drug, while models of recombinant CYP450 enzymes are not fully representative of the complete liver enzyme profile. Additionally, many chemical and antibody inhibitors actually lack sufficient specificity, resulting in little confidence in the results obtained.
To help you overcome these challenges, we provide SilensomesTM HLM. SilensomesTM are validated human-pooled liver microsomes (HLMs) that are chemically and irreversibly inactivated for one specific CYP using mechanism-based inhibitors. SilensomesTM HLM provide you with a simplified, fully characterized pre-made solution that is ready for CYP phenotyping, resulting in more consistent and reliable results.
For more information on the use of SilensomesTM HLM, including case studies, visit our product page.