Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients

Figures & data

Table 1 Gradient elution for HPLC–MS

Time, minutes	Mobile phase A, % (V/V)	Mobile phase B, % (V/V)
0	90	10
1.5	90	10
2	80	40
8.5	30	70
12	95	5
14	90	10

Abbreviation: HPLC–MS, high-performance liquid chromatography with mass spectrometry.

Table 2 Analytical parameters for HPLC–MS

Analyte	Polarity	Precursor (m/z)	Product (m/z)	Collision energy (V)
Omeprazole	+	346.1	346.1	30
5-hydroxyomeprazole	+	362.1	362.1	30
Carbamazepine (internal standard)	+	237.1	194.0	30

Abbreviation: HPLC–MS, high-performance liquid chromatography with mass spectrometry.

Table 3 Frequency of CYP2C19 polymorphisms in peptic ulcer patients

Predicted CYP2C19 phenotype	CYP2C19 genotype	Patients (n)	Frequency (%)
EMs	*1/*1	27	45.8
	*1/*2	10	16.9
IMs	*2/*17	3	5.1
	*3/*17	1	1.7
PMs	*2/*2	2	3.4
UMs	*1/*17	15	25.4
	*17/*17	1	1.7
Total		59	100.0

Abbreviations: EMs, extensive metabolizers; IMs, intermediate metabolizers; PMs, poor metabolizers; UMs, ultrarapid metabolizers.

Table 4 Frequency of CYP2C19 genotype in peptic ulcer patients

CYP2C19 polymorphism	Genotype	Number of patients	Frequency (%)	Hardy–Weinberg equilibrium
CYP2C19*2	GG	44	74.6	χ^2=0.67, p=0.41
	GA	13	22.0
	AA	2	3.4
CYP2C19*17	CC	39	66.1	χ^2=0.60, p=0.44
	CT	19	32.2
	TT	1	1.7
CYP2C19*3	GG	58	98.3	χ^2=0.004, p=0.94
	GA	1	1.7
	AA	0	0

Table 5 Urine metabolic ratio and phenotypes predicted on the basis of CYP2C19 genotypes in peptic ulcer patients

Parameter	Predicted CYP2C19 phenotype
	EMs		UMs		IMs+PMs		Total
	Median	Percentiles (25%–75%)	Median	Percentiles (25%–75%)	Median	Percentiles (25%–75%)	Median	Percentiles (25%–75%)
Metabolic ratio	1.03	0.69–1.36	1.95	1.33–2.68	1.40	0.78–2.13	1.26	0.82–1.99
	EMs/UMs		EMs/IMs+PMs		UMs/IMs+PMs		EMs/UMs/IMs+PMs
Mean rank	17.3	30.0	19.6	26.0	19.0	14.0	22.9 44.4	31.5
Test	Mann–Whitney U test	p-value	Mann–Whitney U test	p-value	Mann–Whitney U test	p-value	Kruskal–Wallis test	p-value
Metabolic ratio	89	0.001	151	0.105	88	0.132	χ^2=10.6, df=2	0.005

Note: Bold values mean that they are p<0.05 and have a statistical significance.

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; PMs, poor metabolizers.

Figure 1 Urine metabolic ratio of omeprazole in patients with predicted CYP2C19 phenotypes based on CYP2C19 genotypes.

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; PMs, poor metabolizers.