Antihypertensive Effect Of Amlodipine In Co-Administration With Omeprazole In Patients With Hypertension And Acid-Related Disorders: Cytochrome P450-Associated Aspects

Figures & data

Table 1 CYP2C19 Genetic Polymorphisms Frequency In Patients With Hypertension And ARD

Predicted CYP2C19 Phenotype	CYP2C19 Genotype	Patients (n)	Frequency (%)
EMs	CYP2C19 *1/*1	21	41.2
UMs	CYP2C19 *1/*17	15	29.4
	CYP2C19 *17/*17	3	5.9
IMs	CYP2C19 *1/*2	8	15.7
	CYP2C19 *2/*17	3	5.9
	CYP2C19 *1/*3	1	1.9
Total		51	100

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

Figure 1 Predicted CYP2C19 phenotype of patients with hypertension and ARD.

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

Table 2 CYP3A4 Activity In Patients With Hypertension And ARD

6 Beta-OHC/C	Mean 1	EMs 2	IMs 3	UMs 4	p-value (Mann–Whitney Test)
					3 vs 1	3 vs 2	3 vs 4
Baseline	1.09 [0.79; 1.30]	1.08 [1.02; 1.23]	1.11 [0.96; 1.35]	1.09 [0.86; 1.31]	0.07	0.07	0.07
Endpoint	0.92 [0.69; 1.09]	0.97 [0.70; 1.28]	0.81 [0.69; 0.93]	0.98 [0.60; 1.14]	0.07	0.08	0.08
Dynamics, ∆	0.17 [0.13; 0.24]	0.11 [0.09; 0.15]	0.30 [0.26; 0.35]	0.11 [0.06; 0.15]	0.05	0.04	0.04
Dynamics, ∆%	15.60 [12.49; 18.17]	10.20 [6.00; 14.65]	27.10 [24.26; 29.34]	10.09 [8.62; 13.85]	0.04	0.04	0.03
p-value	0.05	0.05	0.03	0.05

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; 6 beta-OHC/C, 6-β-hydroxycortisol/cortisol.

Figure 2 6β-hydroxycortisol/cortisol ratio decrease after two weeks of omeprazole + amlodipine treatment (dynamics, ∆%).

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

Table 3 The Dynamics Of OBPM Results In Patients Taking A Combination Of Amlodipine And Omeprazole

		Group Average 1	EMs 2	IMs 3	UMs 4	p-value
						3 vs 1	3 vs 2	3 vs 4
Office SBP, mm Hg	Baseline	137.84	136.90	137.65	138.92
	Endpoint	122.50	123.60	116.40	126.40	0.04	0.04	0.04
	Dynamics, ∆	14.90	13.20	19.90	12.50	0.04	0.04	0.03
	Dynamics, ∆%	11.13	9.65	14.70	8.92	0.04	0.04	0.03
p-value inside the group		0.04	0.04	0.04	0.04
Office DBP, mm Hg	Baseline	87.52	89.51	87.83	85.22
	Endpoint	81.06	81.40	79.50	81.30	0.06	0.06	0.06
	Dynamics, ∆	6.44	8.11	8.30	3.93	0.04	0.06	0.03
	Dynamics, ∆%	7.36	9.05	9.48	4.57	0.04	0.06	0.03
p-value inside the group		0.04	0.04	0.03	0.04
Heart rate, beats per minute	Baseline	77.90	77.88	78.60	77.50
	Endpoint	72.23	72.64	71.80	72.30	0.07	0.07	0.07
	Dynamics, ∆	72.23	72.64	71.80	72.30	0.06	0.06	0.06
	Dynamics, ∆%	7.40	6.60	8.65	6.70	0.06	0.06	0.06
p-value inside the group		0.04	0.04	0.03	0.04

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Figure 3 OBPM decrease in patients after two weeks of omeprazole + amlodipine treatment (dynamics, ∆).

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Table 4 The Dynamics Of ABPM Results In Patients Taking A Combination Of Amlodipine And Omeprazole

		Group Average 1	EMs 2	IMs 3	UMs 4	p-value (Mann–Whitney Test)
						3 vs 1	3 vs 2	3 vs 4
24 hr SBP, mm Hg	Baseline	134.30	134.50	132.70	135.60
	Endpoint	122.50	123.40	117.50	126.70	0.04	0.04	0.03
	Dynamics, ∆	11.80	11.40	14.70	9.20	0.05	0.04	0.03
	Dynamics, ∆%	8.10	8.30	10.65	6.11	0.05	0.04	0.03
p-value inside the group		0.04	0.04	0.03	0.04
24 hr DBP, mm Hg	Baseline	86.70	85.70	86.70	85.72
	Endpoint	78.41	79.90	75.50	79.85	0.06	0.05	0.04
	Dynamics, ∆	8.30	5.80	11.72	5.90	0.04	0.03	0.03
	Dynamics, ∆%	9.50	6.70	12.91	6.80	0.04	0.03	0.03
p-value inside the group		0.04	0.04	0.04	0.04
Daytime SBP, mm Hg	Baseline	137.60	137.70	136.90	138.10
	Endpoint	126.90	129.50	121.60	129.50	0.04	0.04	0.04
	Dynamics, ∆	10.70	8.20	15.30	8.60	0.04	0.04	0.04
	Dynamics, ∆%	7.23	5.50	10.40	5.80	0.04	0.04	0.04
p-value inside the group		0.04	0.04	0.04	0.04
Nighttime SBP, mm Hg	Baseline	131.20	132.34	130.50	130.70
	Endpoint	124.50	125.50	120.40	127.60	0.04	0.04	0.04
	Dynamics, ∆	6.61	6.84	9.9	3.10	0.04	0.04	0.04
	Dynamics, ∆%	5.20	5.20	7.50	2.30	0.04	0.04	0.04
p-value inside the group		0.04	0.04	0.04	0.04
Daytime DBP, mm Hg	Baseline	93.93	92.34	94.50	95.10
	Endpoint	83.60	83.36	80.70	86.70	0.06	0.04	0.04
	Dynamics, ∆	10.38	8.94	13.80	8.40	0.06	0.04	0.04
	Dynamics, ∆%	11.20	9.60	14.60	8.80	0.06	0.04	0.04
p-value inside the group		0.04	0.04	0.02	0.04
Nighttime DBP, mm Hg	Baseline	85.80	86.70	85.70	84.89
	Endpoint	76.80	77.80	74.50	78.80	0.05	0.05	0.04
	Dynamics, ∆	9.20	8.90	11.20	6.80	0.05	0.05	0.04
	Dynamics, ∆%	10.48	10.26	13.06	8.00	0.05	0.05	0.04
p-value inside the group		0.04	0.04	0.04	0.04
24 hr heart rate, beats per minute	Baseline	74.50	73.34	74.50	74.40	0.06	0.06	0.06
	Endpoint	71.54	70.23	71.20	73.20	0.06	0.06	0.06
	Dynamics, ∆	3.10	3.11	3.30	1.20	0.06	0.06	0.05
	Dynamics, ∆%	4.02	4.24	4.40	1.60	0.06	0.06	0.05
p-value inside the group		0.06	0.06	0.06	0.06

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Figure 4 OBPM and ABPM decrease in patients after two weeks of omeprazole + amlodipine treatment (dynamics, ∆).

Abbreviations: EMs, extensive metabolizers; UMs, ultrarapid metabolizers; IMs, intermediate metabolizers; SBP, systolic blood pressure; DBP, diastolic blood pressure.