Effects of the CYP3A5 genotype on omeprazole sulfoxidation in CYP2C19 PMs.
OBJECTIVE
Omeprazole is metabolized by the two cytochrome P450 isoforms, CYP3A (sulfoxidation) and CYP2C 19 (hydroxydation). The aim of this study was to determine whether the CYP3A5 genotype is an important determinant of inter-individual variability of total CYP3A activity in vivo.


METHODS
Plasma levels of omeprazole and omeprazole sulfone were analyzed by high-performance liquid chromatography in blood samples drawn 4-5 h after 43 CYP2C19 poor metabolizers (PMs) had ingested a single oral 40 mg dose of omeprazole. The CYP3A5*3 allele was identified using a PCR-restriction fragment length polymorphism assay.


RESULTS
Among the 43 CYP2C19 PMs, 24 were CYP3A5*3/*3 carriers and 19 were CYP3A5*1 carriers (CYP3A5*I/*I in one subject and CYP3A5*1/*3 in 18 subjects). No significant difference was found between the mean log10 (metabolic ratio) of the CYP3A5*3/*3 carriers (0.314 +/- 0.369) and CYP3A5*1 carriers (0.330 +/- 0.313).


CONCLUSIONS
The CYP3A5 genotype was not an important factor underlying the inter-individual variation in the metabolic ratio of omeprazole to omeprazole sulfone in our study cohort, although genotype can be considered to be responsible for the inter-individual variation of many CYP3A substrates in vivo.
Sugimoto
Katsuyoshi
K
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. chama@cc.hirosaki-u.ac.jp
Uno
Tsukasa
T
Tateishi
Tomonori
T
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000378:metabolism*
C040450:omeprazole sulfone; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D009853:Omeprazole