Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding

Abstract

The combined presence of CYP2C8*3 and CYP2C9*2 (CYP2C8*3+CYP2C9*2 genotype), is a relevant determinant in the risk to develop gastrointestinal bleeding in patients receiving NSAID that are CYP2C8/9 substrates.

Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole

“…The SNP frequencies observed in the study group are consistent with those previously described in healthy Spaniards subjects [20,[25][26][27][28][29] and are at…”

Confirmation That Cytochrome P450 2C8 (CYP2C8) Plays a Minor Role in (S)-(+)- and (R)-(-)-Ibuprofen Hydroxylation in Vitro

“…At a higher IBU concentration (500 M), the same inhibitors were less able to inhibit the 2-hydroxylation of There has been continued interest in the safety and ADME properties of cyclooxygenase inhibitors. This interest has extended to 2-(4-isobutylphenyl)propionic acid (ibuprofen, IBU), which is administered as a racemic mixture of (S)-(ϩ)-and (R)-(Ϫ)-enantiomers (Rodrigues, 2005;Agúndez et al, 2007;Pilotto et al, 2007;Blanco et al, 2008). The metabolism of both enantiomers is complex and involves direct (acyl) glucuronidation, 2-hydroxylation, and 3-hydroxylation (methyl hydroxylation) (Fig.…”

“…However, hydroxylation of both enantiomers has also been measured with rCYP2C8 and other P450s (CYP3A4 and CYP2C19) (Leeman et al, 1993;Hamman et al, 1997;McGinnity et al, 2000). Such data have led various groups to conclude that both CYP2C forms catalyze the oxidative metabolism of IBU, and attempts have been made to evaluate the impact of both CYP2C9 and CYP2C8 genotype on the PK, pharmacodynamics, and side-effect profile of IBU enantiomers (Kirchheiner et al, 2002;Garcia-Martin et al, 2004; Martinez et al, 2005;Pilotto et al, 2007;Blanco et al, 2008). Clinical drug interaction studies with known inhibitors of CYP2C9 (e.g., fluconazole) and CYP2C8 (e.g., gemfibrozil) have been conducted also (Hynninen et al, 2006;Tornio et al, 2007).…”

Effect of theCYP2C8Genotype on the Pharmacokinetics and Pharmacodynamics of Repaglinide

“…Because CYP2C9*2 is associated with reduced enzymatic activity to most substrates and there is some overlap between substrate recognition for CYP2C8 and CYP2C9, this linkage may contribute to clinical relevance of the CYP2C8*3 variant. The role of the CYP2C8*3 polymorphism has been explored in studies with various commonly prescribed pharmaceuticals, such as rosiglitazone, ibuprofen, or paclitaxel (Kirchheiner et al, 2006;Blanco et al, 2008;Gréen et al, 2009). …”