Effect of omeprazole on antihypertensive efficacy of amlodipine in patients with comorbid pathology – arterial hypertension and acid-dependent disease
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Chair of medical and social assessment, urgent and ambulatory care. First Moscow State Medical University named after I. M. Sechenov, Moscow, Russia
Online publish date: 2018-05-27
Publish date: 2018-05-27
Electron J Gen Med 2018;15(4):em61
The problem of drug interactions is increasingly important today because they may induce serious adverse events as well as interfere with efficacy of pharmacotherapy. Combinations of drugs are most often prescribed to patients presenting with comorbid pathology. The incidence of a combination of arterial hypertension (AH) and acid-dependent diseases (ADDs) varies widely ranging from 11.6 to 50%. One of combinations of drugs prescribed to such patients is a combination of calcium channel blocker amlodipine and proton pump inhibitor omeprazole. The latter in the human body undergoes biotransformation mediated at the level of cytochrome P450 by isoenzymes CYP2C19 and CYP3A4. Amlodipine is a substrate of the isoenzyme CYP3A4, which increases the probability of the development of interaction between these drugs. The purpose of our study was to investigate antihypertensive efficacy of amlodipine in patients suffering from arterial hypertension combined with acid-dependent diseases and additionally taking omeprazole.

Study included a total of 150 patients with AH and ADD. Antihypertensive therapy was evaluated by means of office measuring of arterial pressure (AP) and circadian monitoring of AP (CMAP). The followed-up patients with AH and ADD were divided into 2 groups. Group One was composed of hypertensive patients undergoing pharmacotherapy with 10 mg amlodipine, whose condition required due to exacerbation of ADD administration of omeprazole at a dose of 20 mg for a period from 3 to 4 weeks. Group Two comprised hypertensive patients receiving antihypertensive therapy consisting of 10 mg amlodipine, who were found to have remission of acid-dependent diseases, with no additional medication taken.

The obtained findings demonstrated that one of the commonly used drug combinations in treatment of patients with AH and ADD in ambulatory conditions was a combination of omeprazole and amlodipine, accounting for 7.1%. The results of office measurement of arterial pressure (AP) 2 weeks after initiating pharmacotherapy with omeprazole in patients with AH and ADD demonstrated that the patients receiving omeprazole in addition to antihypertensive therapy were found to have a statistically significant decrease in systolic arterial pressure (SAP) and statistically significantly more pronounced dynamics of a decrease in diastolic arterial pressure (SAP) (p<0.05) compared with those not receiving therapy with omeprazole. Also, in the group of patients taking omeprazole, the findings of circadian monitoring of blood pressure (CMAP) showed a statistically significant decrease in average circadian SAP, average circadian DAP, mean value of daytime SAP and mean value of nighttime SAP (p<0.05).

The obtained findings demonstrated that simultaneous prescription of amlodipine and omeprazole to patients with concomitant pathology, i.e., AH and ADD, turned out to enhance the antihypertensive affect of amlodipine, which probably resulted from substrate competition of amlodipine and omeprazole at the level isoenzyme CYP 3A4 of cytochrome P450.

1. Khlynova OV, Tyev AV, Berseneva LN. Problem of comorbidity with regard for the state of the cardiovascular system in patients with arterial hypertension and acid-dependent diseases. Kazan Medical Journal.2003; 1: 80-6.
2. Vertkin AL, Skotnikov AS. Comorbidity. Attending Physician. 2013;6:6-9.
3. Ovchinnikova EA. Role of monitoring of safety of drugs in solving the problem of their rational use. Good Clinical Practice. 2003;4:88-95.
4. Sizova ZhM, Shikh EV., Baichorov IKh. Polyprogmasia and drug interaction in treatment of comorbid patients with arterial hypertension an ambulatory-polyclinical practice. Polyclinic. Cardiology. 2015;1:13-8.
5. Clinical Pharmacology: manual. Under the editorship of V. G. Kukes and D. A. Sychev. Moscow: GEOTAR-Media; 2015.
6. Kukes VG, Grachev SV, Sychev SV, Ramenskaya GV. Metabolism of Drugs. Scientific Grounds of Personified Medicine. Moscow: GEOTAR-Media; 2008.
7. Andersson TB, Ahlström M. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos.2004 Aug;32(8):821–27. https://doi.org/10.1124/dmd.32... PMid:15258107.
8. Howden CW. Clinical pharmacology of omeprazole. Clin Pharmacokinet.1991;20:38–49. https://doi.org/10.2165/000030... PMid:2029801.
9. Leushina EA. Chicherina EN. Arterial hypertension and gastric motor-evacuatory disorders. Vyatka Medical Review.2012;3:50-65.
10. Butov MA. On aetiology and pathogenesis of peptic ulcer. Experimental and Clinical Gastroenterology. 2003;6:5-9.
11. Kokarovtseva LV, Tuev AV, Khlynova OV. Structural and functional remodelling of the heart in patients with combination of hypertension and gastroesophageal reflux disease. Perm Medical J. 2008;5(25):65-70.
12. Samsonov AA, Kazyulin AN, Salman IK, Lebedeva EG. Role of vascular pathology in pathogenesis of peptic ulcer disease. Archives of Internal Medicine.1992;64(2):138-141.
13. Krylov AA. On the problem of compatibility of diseases. Clin. Med. 2000;1:56-68.
14. Smirnova LE. On the problem of comorbidity of ulcerative-erosive gastroduodenal lesions and arterial hypertension. Clin. Med. 2003;3:9-15.
15. Smirnova LE, Shpak LV, Vinogradov VF. Peculiarities of a comorbid course of ulcerative-erosive gastroduodenal lesions and arterial hypertension. Clin. Med. 2005;4:43-54.
16. Leonova MV. Genetic polymorphism of CYP2C19 – a predictor of clinical efficacy of proton pump inhibitors. General Medicine. Clinical Pharmacology. 2015;4:30-39.
17. Lopina OD, Serebrova SYu. Main pharmacokinetic characteristics of proton pump inhibitors and efficacy of their action. Manual for physicians; 2016.
18. Kuo CH, Lu CY, Shih HY. CYP2C19 polymorphism influences Helicobacter pylori eradication. World J. Gastroenterol. 2014;20(43):16029-16036. https://doi.org/10.3748/wjg.v2... PMid:25473155 PMCid:PMC4239489.
19. Li WW, Wallhagen MI, Froelicher ES. Hypertension control, predictors for medication adherence and gender differences in older Chinese immigrants. J Adv Nurs. 2008 Feb;61(3):326-335. https://doi.org/10.1111/j.1365... PMid:18197867.
20. Morozova TV, Sychev DA, Shikh NV. Pharmacogenetic approaches to predicting efficacy and safety of amlodipine in hypertensive patients. Attending Physician. 2016;3:77-82.
21. Morozava TE, Andrushchishina TB. Modern aspects of pharmacotherapy of arterial hypertension: possibilities of amlodipine. Attending Physician. 2013;2:7-12.
22. Leonova MV. Clinical pharmacology and clinical efficacy of amlodipine. Data of evidence-based medicine. Medical Council. 2014;12:14-21.
23. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf.2014, Apr;37(4):201–211. https://doi.org/10.1007/s40264... PMid:24550106 PMCid:PMC3975086.
24. Shikh EV, Sychev DA. Pantoprazole – safety in drug-drug interaction. Russian Journal of Gastroenterology, Hepatology and Coloproctology. 2012;22(5):4-12.
25. Cheng JW, Frishman WH, Aronow WS. Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions. Dis Mon. 2010 Mar;56(3):163-179. https://doi.org/10.1016/j.disa... PMid:20189501.