Contribution of CYP2C19 and CYP3A4 to the formation of the active nortilidine from the prodrug tilidine.

ABSTRACT:

What is already known about this subject

The analgesic activity of tilidine is mediated by its active metabolite, nortilidine, which easily penetrates the blood-brain barrier and binds to the µ-opioid receptor as a potent agonist. Tilidine undergoes an extensive first-pass metabolism, which has been suggested to be mediated by CYP3A4 and CYP2C19; furthermore, strong inhibition of CYP3A4 and CYP2C19 by voriconazole increased exposure of nortilidine, probably by inhibition of further metabolism. The novel CYP2C19 gene variant CYP2C19*17 causes ultrarapid drug metabolism, in contrast to the *2 and *3 variants, which result in impaired drug metabolism.

What this study adds

Using a panel study with CYP2C19 ultrarapid and poor metabolizers, a major contribution of polymorphic CYP2

SUBMITTER: Grun B 

PROVIDER: S-EPMC3495150 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature