Comparative analysis of amlodipine and lercanidipine: mechanisms, limitations, and prospects of combined antihypertensive therapy

Background.Arterial hypertension remains a leading factor in cardiovascular mortality.Fixed-dose combinations provide long-term blood pressure control and increase adherence to therapy.Amlodipine is the pharmacokinetic standard for fixed-dose combinations due to its long half-life and stable exposure, whereas lercanidipine -a third-generation drug with better tolerabilityremains underrepresented in combination regimens. Aim of the study.To compare the pharmacokinetic, pharmacodynamic, and clinical characteristics of amlodipine and lercanidipine, and to substantiate the role of lercanidipine in combination antihypertensive therapy within rationally designed fixed-dose combinations. Materials and methods.A structured literature review (according to international standards for the preparation of systematic reviews) was conducted in the scientific literature databases PubMed, Scopus, Web of Science, and Cochrane Library for the years 2020-2025.50 sources were selected after screening 847 records.The design encompassed three stages: comparison of drug profiles, analysis of microcirculatory mechanisms, and the development of a physiologically based pharmacokinetic protocol.Results.Amlodipine (half-life of 30-50 hours) is minimally affected by food and metabolism by the cytochrome P450 3A4 isoenzyme, and has a powerful evidence base from large-scale clinical trials.Lercanidipine provides a 24-hour effect due to a membrane depot and is characterized by a lower incidence of peripheral edema (9 percent versus 19 percent).Dependence on the cytochrome P450 3A4 isoenzyme and a pronounced effect of food intake limit its use in fixed-dose combinations.The combination with renin-angiotensinaldosterone system blockers neutralizes the residual risk of edema through postcapillary vasodilation and provides a synergistic blood pressure reduction without unwanted pharmacokinetic interactions.Conclusions.Amlodipine remains the standard for combination therapy.Physiologically based pharmacokinetic modeling and optimized dosage forms are capable of overcoming the pharmacokinetic limitations of lercanidipine and expanding its role in fixeddose combinations.