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.
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.
Authors: T Aoyama; S Yamano; D J Waxman; D P Lapenson; U A Meyer; V Fischer; R Tyndale; T Inaba; W Kalow; H V Gelboin Journal: J Biol Chem Date: 1989-06-25 Impact factor: 5.157
Authors: Eric Thervet; Dany Anglicheau; Barry King; Marie-Hélène Schlageter; Bruno Cassinat; Philippe Beaune; Christophe Legendre; Ann K Daly Journal: Transplantation Date: 2003-10-27 Impact factor: 4.939
Authors: E D Kharasch; A Walker; N Isoherranen; C Hoffer; P Sheffels; K Thummel; D Whittington; D Ensign Journal: Clin Pharmacol Ther Date: 2007-06-06 Impact factor: 6.875
Authors: T Andersson; J O Miners; M E Veronese; W Tassaneeyakul; W Tassaneeyakul; U A Meyer; D J Birkett Journal: Br J Clin Pharmacol Date: 1993-12 Impact factor: 4.335
Authors: V Michaud; E Ogburn; N Thong; A O Aregbe; T C Quigg; D A Flockhart; Z Desta Journal: Clin Pharmacol Ther Date: 2012-02-08 Impact factor: 6.875
Authors: Natalia P Denisenko; Dmitriy A Sychev; Zhanna M Sizova; Valeriy V Smirnov; Kristina A Ryzhikova; Zhannet A Sozaeva; Elena A Grishina Journal: Pharmgenomics Pers Med Date: 2018-06-18