In vitro Enzyme Induction

In vitro Enzyme Induction

Enzyme induction can increase the metabolic clearance of a concomitantly administered drug, resulting in reduced efficacy, which may comprise the therapeutic effectiveness of a drug. As such, the FDA and other regulatory agencies recognize enzyme induction as a potential cause of drug-drug interactions.

KaLy-Cell excels in in vitro regulatory enzyme induction studies in primary cultures of human hepatocytes (the "gold standard"), which are conducted in accordance with the Regulatory Agencies recommendation. Induction is evaluated based on changes in gene expression (RT-qPCR analysis of mRNA levels) and changes in enzyme activity determined in the hepatocytes in situ. Exposure of cells to drug is also measured by LC/MS of parent concentration. You can be certain that our strict selection criteria for the cultures used in our induction studies ensure reliable results.

Mainly focused on evaluation of induction of major human CYP isoforms, we are also measuring major human UGT and SULT isoforms. In particular, we offer measurement of thyroxine-UGT activity in hepatocytes in control and inducer-treated hepatocytes.

KaLy-Cell also propose in in vitro screening induction studies in primary cultures of human and animal hepatocytes, these studies are customized according to Sponsor request.

We provide:

• Highly reproducible, accurate data – validated and used by pharmaceutical, biotechnology, agrochemical and cosmetics companies, and academic organizations.

• Delivery of data within several weeks at reception of compounds, to fit in with the make-test timelines in drug discovery. A number of different reporting options are available.

• Attention to good quality customer care, with highly trained Scientists on hand to explain results and suggest the most appropriate experimental strategy.

• Flexibility – studies can be tailored to our customers’ specific requirements.

• Regulations – our services maintain and comply with regulatory guidelines providing constant confidence in the data.

Screening for CYP induction

Our contract service assesses in vitro screening studies of CYP induction in cryopreserved hepatocytes from various species  

• Incubations of plated cryopreserved hepatocytes (e.g. human, monkey, dog, minipig, rat and mouse)
• Incubations in parallel of reference inducers as positive controls to check for responsiveness of the test system (positive controls)
• Daily incubations for 48h (or 72h)
• mRNA expression by RT-qPCR
• Full data summary

Regulatory CYP and UGT induction

KaLy-Cell excels in in vitro regulatory enzyme induction studies in primary cultures of human hepatocytes (the "gold standard"), which are conducted in accordance with the Regulatory Agencies recommendation.

• Incubations of plated human hepatocytes (from 3 donors), pre-characterized for response to positive control inducers
• Induction is evaluated based on changes in gene expression (RT-qPCR analysis of mRNA levels) after a daily incubation for 48h
• Changes in enzyme activity can in addition be determined in the hepatocytes in situ by incubating cell monolayers with a cocktail of CYP substrates and measuring CYP-specific products by LC/MS
• Exposure of cells to drug is also measured by LC/MS of parent concentration.
• Calculations: fold of control, % of positive control, EC50 and Emax determination when possible
• Full data reporting
• You can be certain that our strict selection criteria for the cultures used in our induction studies ensure reliable results.