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ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors
- Source :
- Journal of Cardiovascular Pharmacology and Therapeutics. 22:374-386
- Publication Year :
- 2017
- Publisher :
- SAGE Publications, 2017.
-
Abstract
- Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient’s response. Objectives: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the “ACE phenotype”—for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. Methods: The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient’s blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Results: Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Conclusion: Due to the fact that “20% of patients do not respond to ACEI by blood pressure drop,” the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.
- Subjects :
- 0301 basic medicine
Pharmacogenomic Variants
Sodium Chloride Symporter Inhibitors
Drug Resistance
Tetrazoles
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
030204 cardiovascular system & hematology
Pharmacology
0302 clinical medicine
Hydrochlorothiazide
Enalapril
Medicine
Pharmacology (medical)
Precision Medicine
Personalized therapy
Cross-Over Studies
biology
Phenotype
Treatment Outcome
Hypertension
Drug Therapy, Combination
Drug Monitoring
Cardiology and Cardiovascular Medicine
medicine.drug
Genotype
Peptidyl-Dipeptidase A
03 medical and health sciences
Double-Blind Method
Predictive Value of Tests
Humans
Ace activity
Antihypertensive Agents
business.industry
Patient Selection
Biphenyl Compounds
Angiotensin-converting enzyme
Pharmacogenomic Testing
Candesartan
030104 developmental biology
Blood pressure
Pharmacogenetics
ACE inhibitor
biology.protein
Benzimidazoles
business
Angiotensin II Type 1 Receptor Blockers
Subjects
Details
- ISSN :
- 19404034 and 10742484
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Pharmacology and Therapeutics
- Accession number :
- edsair.doi.dedup.....f753c72083f30ee52aedb5a39aa90819