Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2.
OBJECTIVE
To evaluate the effect of the CYP1A2*1C and CYP1A2*1F polymorphisms on the inducibility of CYP1A2 by omeprazole in healthy subjects.


METHODS
Mutations of CYP2C19 and CYP1A2 were identified by PCR-RFLP. Omeprazole, 120 mg day-1, was given to 12 extensive metabolizers (EM) with respect to CYP2C19 (six CYP1A2*1F/CYP1A2*1F and six CYP1A2*1C/CYP1A2*1F of CYP1A2) for 7 days. CYP1A2 activity was determined on three occasions, namely on day 1, day 9 and day 16 using the caffeine plasma index (the ratio of the concentrations of paraxanthine to caffeine), 6 h after oral administration of 200 mg caffeine.


RESULTS
There was a significant difference (P = 0.002) between the caffeine ratios for CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes on day 9, but not on day 1 or day 16 (P > 0.05). The changes in the ratios from day 9 to day 1 (48% +/- 20%vs 19% +/- 20%) and from day 9 to day 16 (50% +/- 31%vs 15% +/- 22%) were significantly different (P < 0.05) between the CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes.


CONCLUSIONS
The CYP1A2*1C and CYP1A2*1F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.
Han
Xing-Mei
XM
Pharmacogenetics Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan 410078, China.
Ouyang
Dong-Sheng
DS
Chen
Xiao-Ping
XP
Shu
Yan
Y
Jiang
Chang-Hong
CH
Tan
Zhi-Rong
ZR
Zhou
Hong-Hao
HH
D000328:Adult; D002110:Caffeine / Q000097:blood; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D009853:Omeprazole