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Effect of gender and CYP2C9 and CYP2C8 polymorphisms on the pharmacokinetics of ibuprofen enantiomers.

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.