Abstract: Cytochrome P450 (CYP) induction is a major cause of drug-drug interaction. CYP induction increases the elimination of the inducer drug or a co-administered drug which can lead to reduced or complete loss in their efficacy. Primary human hepatocytes are the preferred and most commonly used in vitro model for conducting CYP induction studies. The induction response in hepatocytes can accurately predict the potential for induction in vivo. Induction studies are routinely carried out using both fresh and cryopreserved hepatocytes. Compared to their fresh counterparts, however, cryopreserved human hepatocytes have limited applications due to impaired attachment ability by some (not every lot can plate) and sometimes impaired enzyme activities caused by cryopreservation process; for example, some cryopreserved lots have very low basal CYP450 activities, resulting in very high (non-physiological) fold induction which could provide false DDI information. Since cryopreserved hepatocytes have benefits of being convenient, more available, and able to provide multiple lots for comparison, it is therefore important to develop culture conditions that support recovery, attachment and maintenance of cell morphology and metabolizing enzymes.

It has been shown that extracellular matrix (ECM) based substrata provide a physiological environment that maintains differentiation character and supports key cellular functions; specifically for hepatocytes, collagen I has been the most popular substratum for attachment and induction assays. In this seminar, we discuss the benefits of a more complicated matrix, BD Matrigel Matrix, on attachment, morphology, and enzyme activities of cryopreserved hepatocytes.

Abstract: The appearance of the USFDA‘s draft guidance document for drug interaction studies in September of 2006 has prompted significant discussion among industry researchers. The recommendations provided for testing metabolism-based drug interactions has reinforced much of the dogma established over the decade since the previous guidance for industry appeared. The current draft guidance provides recommendations for a number of in vitro as well as clinical drug-drug interaction testing. The science for testing in vitro cytochrome P450 inhibition has advanced to the point where we can identify with relatively high confidence compounds with elevated risk to cause metabolism-based drug interaction, providing that a suitable strategy is implemented. This presentation reviews the essential elements of a testing program that aligns with the agency‘s guidance and also reviews options for BD Gentest^sm Cytochrome P450 Inhibition Services with a focus on reversible and time-dependent inhibition.

NOTE: This Webinar was given previously in 2008 and is being repeated due to popular demand. The content will be updated to incorporate any updates on regulatory status.

Driving Cellular Communication with the Extracellular Matrix: Optimization of Cell Growth and Differentiation