Effect Of Curcumin On CYP2C9 Activity In Human Being

Background: Curcumin is a plant polyphenol witch is extracted from the Zingiberaceae rhizome of Curcuma longa. Curcumin has a wide range of pharmacological effects, including linked antioxidant, anti-tumor, anti-inflammatory, free radical scavenging, anti-microbial as well as the cardiovascular system, the role of the digestive system. It has become increasingly clarified CYP2C9 is a very important drug metabolizing CYP isoform in human liver. CYP2C9 is principally responsible for the metabolism of a number of clinically important durgs.It is also involved in the metabolic activation of certain pro-drugs and certain pro-carcinogens. CYP2C9 has polymorphisms, of which CYP2C9*3 mutation are major alleles related to alteration of enzyme activity in Asians. Currently, several researchers has found that curcumin is able to increase the activity of CYP2C9 in vitro. However, there is no study about the effect of curcumin on CYP2C9 in vivo that has been reported.Objective: To investigate the effect of curcumin on CYP2C9 activity in vivo.At the same time to explore the relationship between the effect of curcumin on CYP29 and CYP2C9 genotype.Methods: An open, randomize, 2-period study was performed in 14 healthy male volunteers. Tolbutamide (a CYP2C9 substrate) was used as a probe. Genotypes were determined using the PCR-RFLP assay. Suitable subjects have been selected out, including 7 (CYP2C9*1*1) and 7 (CYPC29*1*3) genotype. 14 healthy volunteers were divided into two groups randomly. Two groups were administered by a single oral 500 mg tolbutamide before and after treatment with curcumin for 14 days (n=7).5ml blood samples were collected at Oh, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 6h to12h urine was collected after the 500mg tolbutaminde tablet.Then the collections of tolbutamide and hydroxytolbutamide in blood an urine were determined by HPLC.CYP2C9 activity was measured as the ratio of metabolites(hydroxytolbutamide) extreted in the 0h to 12h urine to the AUC_1-12h of tolbutamide in blood.Results: After 14 days consecutive administration of curcumin, Tmax significantly decreased (2.89±1.50 VS 1.75±0.85). AUC_(0-24) shortened significantly(2820.33±852.69μg.h / ml 2278.05±601.35μg.h / ml , P＜0.05), AUC_(0-∞) shortened significantly ((3482.65±1376.30μg.h / ml VS 2824.12±1059.92μg.h / ml, P＜0.05). And urine _{hydroxymethyl(0-12h)} / blood _AUC(0-12h) significantly increased (13.26±9.57 ml/hVS 16.38±11.76 ml/ h, P＜0.05), which implied that curcumin induced the activity of CYP2C9. There is no significant relationship between the induction and the CYP2C9 genotypes.Conclusion: In conclusion, curcumin is able to significantly induce the activity of CYP2C9 in vivo, while there is no significantly relationship between the inhibition of curcumin on the activity of CYP2C9 and CYP2C9 genotypes. Therefore, it is necessary to pay great attention when the drug interaction occurs between curcumin and CYP2C9 substrates.