Naslov
Non-NADPH Time Dependent Inhibition of Cytochromes P450

Autori
Bojić, Mirza

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Pharmacia / Ademović, Zahida - Sarajevo : Pharmaceutical Society of Federation of Bosnia and Herzegovina, 2015, 160-160

Skup
3rd Congress of Pharmacists of Bosnia and Herzegovina

Mjesto i datum
Sarajevo, Bosna i Hercegovina, 14.05.2015. - 17.05.2015

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cytochrome P450; NADPH; time dependent inhibition

Sažetak
Latest literature review on participation of cytochromes P450 in oxidation-reduction reactions has shown that cytochromes P450 participate in 92-96% metabolic reactions of xenobiotics (1). Most relevant P450s in drug metabolism are 3A4 (27%), 2D6 (13%), 2C9 (10%), 2C19 (9%), and 1A2 (9%). It is interesting that most of the adverse drug reactions can be related to drug-drug interactions most of which consequently involve cytochromes P450. The objective of this work is to assess the importance of time dependent inhibition of cytochromes P450. Cytochromes P450 are most commonly inhibited by competitive inhibition which is reversible or inactivated by mechanism/metabolism based inhibition that is NADPH dependent. The later one tends to be more clinically significant as it is irreversible and requires time to regain normal metabolic activity of the enzyme. However, non- NADPH time dependent inhibition is rarely observed with cytochromes P450. Methods involved in characterization of any type of inhibition include monitoring reaction of marker substrate of particular cytochrome P450 by LC-DAD/MS and if applicable spectrophotometric binding of inhibitor to the enzyme (2). In this presentation approach in characterization of non- NADPH time dependent inhibition that relies on binding titrations and residual activity testing as major tools in analysis of structural features responsible for inhibition, will be shown. Metabolism dependent inhibition is also time dependent but it does not apply vice versa. Thus time dependent inhibition assays should be included in official guidelines on testing potential inhibitors of cytochromes P450 and consequently drug-drug interactions.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Farmacija

POVEZANOST RADA