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Exploring CYP3A4 Inactivation by Lapatinib Through In Vitro Metabolite Characterization

from Sekisui XenoTech

Metabolism-dependent inhibition of cytochrome P450 enzymes has the potential to cause clinically-relevant drug-drug interactions. Alkylamine drugs are known for their propensity to cause CYP inhibition by formation of a metabolite that binds quasi-irreversibly to the ferrous heme iron of the enzyme. The secondary alkylamine drug lapatinib has been linked both to drug-induced liver injury and quasi-irreversible inhibition of CYP3A4. In the present study, in vitro techniques to probe reversibility of enzyme inactivation were combined with metabolite profiling by high-resolution liquid chromatography with accurate mass spectrometry to explore the mechanism of CYP3A4 inactivation associated with lapatinib metabolism.

Key concepts discussed in this webinar will include:
- Insight into metabolism-dependent CYP inhibition by alkylamines
- Utility of in vitro reversibility assays
- Mechanism of CYP3A4 inactivation by the tyrosine kinase inhibitor lapatinib

Download slides: https://www.xenotech.com/scientific-resources/webinar-series/2013/Lapatinib-3A4-Inactivation.aspx

Questions: https://www.xenotech.com/contact-us

Upcoming Webinars: https://www.xenotech.com/scientific-resources/upcoming-webinars

Other Previously Aired Webinars: https://www.xenotech.com/scientific-resources/webinar-series

about 2 years ago

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