CYP2C9 ACTIVITY IN ANKYLOSING SPONDYLITIS PATIENTS TREATED WITH TUMOR NECROSIS FACTOR-ALPHA (TNFα) BLOCKERS

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease. AS is mainly characterized by inflammation, especially increase of the proinflammatory cytokines such as, TNF-α, IL-6, IL-17 and IL-23. Tumor necrosis factor-alpha (TNFα) blockers, for example, etanercept, infliximab, golimumab and adalimumab are used for the treatment of AS. In a previous study, we found that CYP2C9 enzyme activity was lower in AS patients compared to the healthy volunteers. This work purposes to compare the phenotype of CYP2C9 in Anti-TNF user and non-user AS patients.

A total of 32 patients with AS (11 Anti-TNF user, 21 non-users) were recruited in the study. A single 50 mg losartan was given to the participants and 8-hr urine was collected overnight. Then, the urinary concentrations of losartan and its metabolite, E3174, were measured by high-pressure liquid chromatography. Urinary losartan/E3174 metabolic ratio was used as an index of CYP2C9 enzyme activity. Differences in the metabolic ratio of losartan was compared with Mann–Whitney U test.

The mean values of losartan metabolic ratio were 2.14 and 2.33 in Anti-TNF user and non-user AS patients (p=0.51, median and 95% CI: 1.27 [0.92-3.35] and 1.84 [1.48-3.18], respectively).

CYP2C9 enzyme activity was similar in Anti-TNF user and non-user, therefore anti-TNF drugs do not seem to interact with CYP2C9 substrates. 

Keywords

• CYP2C9 ACTIVITY IN ANKYLOSING SPONDYLITIS PATIENTS TREATED WITH TUMOR NECROSIS FACTOR-ALPHA (TNFα) BLOCKERS

Kaynakça

1. Yildirim Beyazit University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey
2. Selçuk University, Faculty of Medicine, Department of Pharmacology, Konya, Turkey
3. Selçuk University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Konya, Turkey
4. Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey