Journal
PHARMACOGENOMICS
Volume 16, Issue 9, Pages 939-948Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/pgs.15.40
Keywords
CYP2C8; CYP2C9; ibuprofen; pharmacokinetics; polymorphisms
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Funding
- Fundacion Teofilo Hernando, Universidad Autonoma de Madrid
- University Autonoma de Madrid (FPI)
- Abbott
- Alter
- Chemo
- Farmalider
- Ferrer
- GlaxoSmithKline
- Janssen-Cilag
- Kern
- Normon
- Novartis
- Servier
- Teva
- Zambon
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Aim: To evaluate the effect of polymorphisms in CYP2C9 and CYP2C8 and gender on the pharmacokinetics of the enantiomeric forms of ibuprofen. Materials & methods: 122 healthy volunteers were genotyped for polymorphisms in CY2C8 and CYP2C9 using real-time PCR. Results:CYP2C8 polymorphisms affected neither R- nor S-ibuprofen. CYP2C9*3 and CYP2C9*2 carriers had a lower S-ibuprofen clearance and a higher S-ibuprofen AUC and half-life. R-ibuprofen clearance was decreased in CYP2C9*3 carriers. Gender affected R-ibuprofen and S-ibuprofen pharmacokinetics. Multiple regression analysis showed that CYP2C9*2, CYP2C9*3 and gender were associated with S-ibuprofen clearance, but only CYP2C9*3 was associated with R-ibuprofen clearance. Conclusion: The pharmacokinetics of S-ibuprofen and R-ibuprofen is affected by CYP2C9 polymorphisms and gender. CYP2C8 polymorphisms do not have a significant role. Original submitted 6 February 2015; Revision submitted 1 April 2015
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