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Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2
Author(s) -
Han XingMei,
Ouyang DongSheng,
Chen XiaoPing,
Shu Yan,
Jiang ChangHong,
Tan ZhiRong,
Zhou HongHao
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.01686.x
Subject(s) - cyp1a2 , paraxanthine , caffeine , omeprazole , cyp2c19 , pharmacology , chemistry , genotype , biology , biochemistry , medicine , metabolism , cytochrome p450 , gene
Aims 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 . Conclusion The CYP1A2 * 1C and CYP1A2 * 1F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.