Pharmacokinetics of Amlodipine in Patients with Arterial Hypertension

Aim. To evaluate the pharmacokinetics of amlodipine in patients with arterial hypertension.

Design. Open cohort study.

Materials and methods. The study included 183 patients, 98 of them with uncontrolled arterial hypertension and 85 with controlled hypertension. All patients regularly took any two antihypertensive drugs (AHD) (lisinopril, amlodipine, valsartan, metoprolol) in combination with indapamide for a month. In the morning, fasting, before taking AHD and 2 hours after taking amlodipine, venous blood samples were taken from all patients to test the concentration of the analyte using high-performance liquid chromatography with tandem mass spectrometry.

Results. In terms of the main concomitant diseases, the patients of the two groups were comparable to each other. Only angina pectoris (p = 0.02) and overweight (p = 0.02) were statistically significantly more common in the pressure–controlled group, and less often — grade 2 obesity (p = 0.002) and acute cerebrovascular accident (p = 0.05). The daily dose of amlodipine in patients with controlled hypertension was significantly (13.9%) lower (p < 0.05) than in participants with uncontrolled hypertension. Both the steadystate concentration of amlodipine and the concentration 2 hours after administration in patients with uncontrolled hypertension were not statistically significantly different from those in patients with controlled hypertension (p > 0.05). In 65.6% of patients with uncontrolled and in 49.4% with controlled hypertension, the concentration of amlodipine was within the therapeutic range (p = 0.03), in 5.2% and 16.5%, respectively, it was above the therapeutic range (p = 0.016), in 29.2% and 34.1%, respectively, — below the therapeutic range (p > 0.05).

Conclusion. Conducting therapeutic drug monitoring and assessing the pharmacokinetics of amlodipine in clinical practice may be useful to improve the effectiveness and safety of therapy.

1. Bulsara K.G., Cassagnol M. Amlodipine. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

2. Wang J.G., Palmer B.F., Vogel Anderson K., Sever P. Amlodipine in the current management of hypertension. J. Clin. Hypertens. (Greenwich). 2023;25(9):801–7. DOI: 10.1111/jch.14709

3. Ferrari R., Pavasini R., Camici P.G., Crea F. et al. Anti-anginal drugs-beliefs and evidence: systematic review covering 50 years of medical treatment. Eur. Heart J. 2019;40(2):190–4. DOI: 10.1093/eurheartj/ehy504

4. Singh J., Elton A., Kwa M. Comparison of various calcium antagonist on vasospastic angina: a systematic review. Open Heart. 2023;10(1):e002179. DOI: 10.1136/openhrt-2022-002179

5. Abernethy D.R., Schwartz J.B. Pharmacokinetics of calcium antagonists under development. Clin. Pharmacokinet. 1988;15(1):1–14. DOI: 10.2165/00003088-198815010-00001

6. Park J.W., Kim K.A., Il Kim Y., Park J.Y. Pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings. Basic Clin. Pharmacol. Toxicol. 2019;125(4): 345–52. DOI: 10.1111/bcpt.13244

7. Dorofeeva M.N., Shikh E.V., Sizova Zh.M., Sychev D.A. et al. Antihypertensive efficacy of amlodipine in patients with arterial hypertension taking omeprazole depending on genetic polymorphism of patients. Russian Journal of Cardiology and Cardiovascular Surgery. 2018;11(2): 45–50. (in Russian). DOI: 10.17116/kardio201811245-50

8. Ates H.C., Roberts J.A., Lipman J., Cass A.E.G. et al. On-site therapeutic drug monitoring. Trends Biotechnol. 2020;38(11):1262–77. DOI: 10.1016/j.tibtech.2020.03.001

9. Punt A.M., Stienstra N.A., van Kleef M.E.A.M., Lafeber M. et al. Screening of cardiovascular agents in plasma with LC-MS/MS: a valuable tool for objective drug adherence assessment. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2019;1121:103– 10. DOI: 10.1016/j.jchromb.2019.05.013

10. Berra E., Pappaccogli M., Cusato J., D'Avolio A. et al. Therapeutic drug monitoring-guided definition of adherence profiles in resistant hypertension and identification of predictors of poor adherence. Br. J. Clin. Pharmacol. 2018;84(11):2535–43. DOI: 10.1111/bcp.13706

11. Seleznev S., Shchulkin A., Mylnikov P., Yakusheva E. et al. Therapeutic drug monitoring in arterial hypertension. J. Pers. Med. 2023;13(5):815. DOI: 10.3390/jpm13050815

12. Regenthal R., Krueger M., Koeppel C., Preiss R. Drug levels: therapeutic and toxic serum/plasma concentrations of common drugs. J. Clin. Monitoring Computing. 1999;15(7–8):529–44. DOI: 10.1023/a:1009935116877

13. Rathore S.S. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871. DOI: 10.1001/jama.289.7.871

14. Groenland E.H., van Kleef M.E.A.M., Bots M.L., Visseren F.L.J. et al. Plasma trough concentrations of antihypertensive drugs for the assessment of treatment adherence: a metaanalysis. Hypertension. 2021;77(1):85–93. DOI: 10.1161/HYPERTENSIONAHA.120.16061

15. Luo Y., Ren L., Jiang M., Chu Y. Anti-hypertensive efficacy of amlodipine dosing during morning versus evening: a metaanalysis. Rev. Cardiovasc. Med. 2019;20(2):91–8. DOI: 10.31083/j.rcm.2019.02.31814

16. Venkateswaran M., Poornima M., Kumar C.V. Adverse drug effects monitoring of amlodipine in a tertiary care hospital. Int. J. Basic Clin. Pharmacol. 2018;7(6):1078–82. DOI: 10.18203/2319-2003.ijbcp20182069

17. Khadka S., Joshi R., Shrestha D.B., Shah D. et al. Amlodipineinduced pedal edema and its relation to other variables in patients at a tertiary level hospital of Kathmandu. Nepal J. Pharm. Technol. 2019;35(2):51–5. DOI: 10.1177/8755122518809005