Klin Farmakol Farm. 2003;17(3):151-157

Lékové interakce na úrovni cytochromů P450 - Část I. Interakce na úrovni CYP3A4

Lucie Kousalová, Jana Baranová, Pavel Anzenbacher
Ústav farmakologie LF UP a FN Olomouc

Tento souhrnný článek popisuje farmakokinetické lékové interakce na úrovni metabolizmu zprostředkovaného cytochromem P450 (CYP) 3A4. CYP3A4 je nejrozšířenější formou všech cytochromů P450 a podílí se na většině známých přeměn léčiv, které probíhají za účasti cytochromů P450. Mezi léčiva, která jsou považována za typické substráty s velkým potenciálem k interakcím, patří většina makrolidových antibiotik (jako erytromycin), azolová antimykotika (itrakonazol, ketokonazol) a blokátory kalciového kanálu s dihydropyridinovou strukturou (např. nifedipin). Lékové interakce na úrovni CYP3A4 jsou způsobeny jak indukcí tohoto enzymu tak inhibicí CYP3A4. Vzhledem k závažnosti případných nežádoucích účinků je třeba při současné medikaci vybírat z nabízených léčiv ty možnosti, kde jsou lékové interakce minimální.

Keywords: drug interactions, cytochromes P450, CYP3A4, inhibition, induction, metabolism.

Published: December 31, 2003  Show citation

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Kousalová L, Baranová J, Anzenbacher P. Lékové interakce na úrovni cytochromů P450 - Část I. Interakce na úrovni CYP3A4. Klin Farmakol Farm. 2003;17(3):151-157.

Tento souhrnný článek popisuje farmakokinetické lékové interakce na úrovni metabolizmu zprostředkovaného cytochromem P450 (CYP) 3A4. CYP3A4 je nejrozšířenější formou všech cytochromů P450 a podílí se na většině známých přeměn léčiv, které probíhají za účasti cytochromů P450. Mezi léčiva, která jsou považována za typické substráty s velkým potenciálem k interakcím, patří většina makrolidových antibiotik (jako erytromycin), azolová antimykotika (itrakonazol, ketokonazol) a blokátory kalciových kanálů s dihydropyridinovou strukturou (např. nifedipin). Lékové interakce na úrovni CYP3A4 jsou způsobeny jak indukcí tohoto enzymu tak inhibicí CYP3A4. Vzhledem k závažnosti případných nežádoucích účinků (zejména nebezpečí maligních arytmií) je třeba při současné medikaci vybírat z nabízených léčiv ty možnosti, kde jsou lékové interakce minimální.

Drug interactions based on metabolism via cytochromes P450 - Part I. Interactions involving CYP3A4

This article describes pharmacokinetic drug interactions based on metabolism mediated by cytochrome P450 (CYP) 3A4. CYP3A4 is the most abundant form of cytochromes P450 and participates in metabolism of the majority of drugs with known metabolic pathways. Among drugs which are taken as typical CYP3A4 substrates with great interacting potential belong most of the macrolide antibiotics (e. g. erythromycin), azole antifungals (itraconazole, ketoconazole), and calcium channel blockers of dihydropyridine structure (as nifedipine). Drug interactions on CYP3A4 level are caused either by induction of this enzyme or by inhibition of CYP3A4. Concerning the relevancy of adverse effects (especially the danger of fatal arrhythmia) it is necessary to select the drugs which have minimum of drug interactions.

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