Lercanidipine hydrochloride

Effects of lercanidipine hydrochloride versus felodipine sustained-release on day-to-day home blood pressure variability.[Pubmed:27779454]

Curr Med Res Opin. 2016 Oct;32(sup2):43-52.

OBJECTIVE: The objective of this study was to compare the effectiveness of lercanidipine with felodipine in patients with mild-to-moderate hypertension on day-to-day home blood pressure variability. METHODS: This is a sub-study of a multicenter, randomized, open-label, parallel group and active controlled clinical trial. Hypertensive patients aged 18-75 (i.e. diastolic blood pressure >/=90 mmHg and <110 mmHg; systolic blood pressure >/=140 mmHg and <180 mmHg) and 24 h mean BP >130/80 mmHg) were eligible for this study. During the study, blood pressure (BP) and heart rate (HR) were recorded. The day-to-day BP variability (BPV) and HR variability (HRV) were obtained by the standard deviation (SD) of daily BP/HR average (of six readings) in 7 days. RESULTS: There were 186 patients (89 and 97 patients in the lercanidipine and felodipine groups, respectively) included in this study. Lercanidipine hydrochloride 10 mg/d and felodipine sustained-release tablets 5 mg/d were given to their respective groups. After 6 weeks of treatment, SD of home BP significantly reduced compared with baseline in both groups (P < .05) while SD of home HR also changed significantly after treatment (P < .05). There was no significant difference in SD of home BPV between the lercanidipine and felodipine groups after treatment. CONCLUSION: Treatment with lercanidipine and felodipine both resulted in reduction of BPV and HRV. There was no significant inter-group difference in reduction of BPV between the groups. Lercanidipine is an effective antihypertensive drug in improving BPV. National clinical trial: NCT01520285.

Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.[Pubmed:24445002]

Colloids Surf B Biointerfaces. 2014 Apr 1;116:81-7.

Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design Lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 +/- 1.5 mV. More than 70% Lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released Lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for Lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension.

Lercanidipine hydrochloride versus felodipine sustained-release for mild-to-moderate hypertension: a multi-center, randomized clinical trial.[Pubmed:25425015]

Curr Med Res Opin. 2015 Jan;31(1):171-6.

OBJECTIVE: Lercanidipine hydrochloride and felodipine sustained-release tablets comparison for the treatment of patients with mild-to-moderate primary hypertension. RESEARCH DESIGN AND METHODS: The study was designed as a multicenter, randomized, open-label, parallel-group clinical trial. A total of 281 adult patients (18-75 years) with a mild-to-moderate primary hypertension diagnosis were randomly assigned, in a 1:1 ratio, to Lercanidipine hydrochloride (n = 139; 81 males) or felodipine sustained-release tablets (n = 142; 87 males). Study duration was 8 weeks, including two run-in weeks and 6 weeks of treatment. MAIN OUTCOME MEASURES: The mean seated diastolic blood pressure (BP) change from baseline to 6 weeks of treatment was the primary endpoint. Main secondary efficacy parameters were: (i) mean seated systolic BP change from baseline to 6 weeks of treatment; (ii) normalization BP rate. The incidence of adverse events was also considered. RESULTS: BP monitoring showed a significant decrease compared with baseline in diastolic BP (lercanidipine: from 96 +/- 4 to 83 +/- 6 mmHg, p < 0.0001; felodipine: from 96 +/- 4 to 82 +/- 5 mmHg, p < 0.0001). The mean systolic BP decreased, when compared with baseline values, by 18 mmHg and 19 mmHg in the lercanidipine and felodipine arm, respectively (p < 0.0001 versus baseline for both comparisons). The normalization rates of BP were 79.5% and 87.2%, in the lercanidipine and felodipine groups, respectively (in-office monitoring; p = n.s.). In total, 73 patients experienced 103 AEs: 26.6% (37/139) in the lercanidipine group and 25.3% (36/142) in the felodipine arm (p = n.s.). The analysis of safety showed no unexpected adverse events. CONCLUSIONS: Although the overall short follow-up of the present study should be taken into account, lercanidipine is an effective and safe treatment option for BP control in adult patients with mild-to-moderate primary hypertension.

A fast, stability-indicating, and validated liquid chromatography method for the purity control of lercanidipine hydrochloride in tablet dosage form.[Pubmed:24959405]

Sci Pharm. 2014 Jan 16;82(2):327-40.

A robust, sensitive, and stability-indicating rapid resolution liquid chromatography method for the simultaneous determination of process impurities and degradation products of Lercanidipine hydrochloride in pharmaceutical dosage form was developed and validated. The chromatographic separation was performed on the Zorbax SB C18 [(50 x 4.6) mm] 1.8 mum column, using gradient elution of a potassium dihydrogen phosphate buffer (pH 3.5, 0.01 M) and acetonitrile. The flow rate was 1.0 ml/min and UV detection was performed at 220 nm. The method was further evaluated for its stability-indicating capability by hydrolytic, oxidative, thermal, thermal with moisture, and photolytic degradation studies. All acceptance criteria of the International Conference on Harmonization guidelines for validation were covered in the method validation. This method can be used for purity control during manufacture and real time stability studies. A shorter run time of 10 minutes and good solution stability for at least 48 hours allowed the quantification of more than 50 samples per day with comparatively lower costs than existing methods.

Molecular mechanisms of vasoselectivity of the 1,4-dihydropyridine lercanidipine.[Pubmed:15155536]

Br J Pharmacol. 2004 May;142(2):275-84.

The effects of (S)- and (R)-lercanidipine on CHO cells stably expressing the cardiac (Ca(v)1.2a) or vascular (Ca(v)1.2b) splice variant of the L-type calcium channel pore subunit were studied, using whole-cell and single-channel patch-clamp measurements. Lercanidipine block of Ca(v)1.2b current was enantioselective. (S)-lercanidipine was 4.1-fold more potent. Experiments using acidic solutions (pH 6.8) revealed a 6.4-fold enhanced inhibitory effect of (S)-lercanidipine compared with physiological conditions (pH 7.4) indicating that the charged form mediates inhibition. At depolarised holding potential (-40 mV), (S)-lercanidipine exhibited a 35-fold greater potency, compared with standard conditions (-80 mV). A comparison of the concentration-dependent inhibition of Ca(v)1.2a with Ca(v)1.2b subunit currents by (S)-lercanidipine revealed only a 1.8-fold difference in IC(50), but the slope of the dose-response curve was much steeper (n(H)=2.3) with Ca(v)1.2a, compared with Ca(v)1.2b (n(H)=0.8). This indicates overlap between agonistic and antagonistic effects, predominant with the cardiac Ca(v)1.2a subunit. This idea is supported by transient stimulatory effects, and a slight leftward shift of the IV curves. These effects were more prominent for Ca(v)1.2a than for Ca(v)1.2b. Single-channel experiments confirmed typical features of calcium channel agonists such as prolonged channel openings, a component of lengthened openings, and an enhanced open probability in the presence of (S)-lercanidipine. Again, these findings were concentration-dependent and more pronounced for Ca(v)1.2a than for Ca(v)1.2b. Our data indicate a splice-variant predominant agonism as a new mechanism contributing to the vasoselectivity of lercanidipine, along with marked voltage-dependence of action.

Lercanidipine : a review of its efficacy in the management of hypertension.[Pubmed:14609358]

Drugs. 2003;63(22):2449-72.

UNLABELLED: Lercanidipine (Zanidip) is a vasoselective dihydropyridine calcium channel antagonist that causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug that exhibits a slower onset and longer duration of action than other calcium channel antagonists. Furthermore, lercanidipine may have antiatherogenic activity unrelated to its antihypertensive effect. In two large, nonblind, noncomparative studies involving approximately 16 000 patients with mild-to-moderate hypertension, systolic blood pressure (BP) [SBP] and diastolic BP (DBP) were significantly reduced after 12 weeks' treatment with lercanidipine 10-20 mg/day. Furthermore, in the largest study, 64% of patients were responders (DBP <90 mm Hg) after 12 weeks of treatment and an additional 32% had their BP normalised (BP <140/90 mm Hg). In comparative trials, lercanidipine 10-20 mg/day was as effective as nifedipine slow release (SR) 20-40 mg twice daily, amlodipine 10 mg/day, felodipine 10-20 mg/day, nifedipine gastrointestinal therapeutic system (GITS) 30-60 mg once daily or verapamil SR 240 mg/day at reducing SBP and DBP in patients with mild-to-moderate hypertension after 2-16 weeks of therapy. In addition, 4 weeks of lercanidipine therapy (10 mg/day) was as effective as captopril 25mg twice daily, atenolol 50 mg/day or hydrochlorothiazide 12.5 mg/day. Lercanidipine 5-30 mg/day effectively decreased BP in elderly patients (aged >60 years) with mild-to-moderate hypertension or isolated systolic hypertension to the same extent as amlodipine 5-10 mg/day, nifedipine GITS 30-60 mg/day or lacidipine 2-4 mg/day after 24-26 weeks of therapy. In addition, a limited number of studies suggest that lercanidipine may have antihypertensive efficacy in patients with severe or resistant hypertension, in hypertensive patients with type 2 diabetes mellitus and in postmenopausal women with mild-to-moderate essential hypertension. Lercanidipine is well tolerated, with most treatment-emergent events related to vasodilation. Common adverse events included headache, flushing and peripheral oedema. Importantly, the incidence of vasodilatory oedema was significantly lower in patients receiving lercanidipine than in those receiving some other calcium channel antagonists. CONCLUSION: Once-daily lercanidipine is an effective and well tolerated antihypertensive agent in patients with mild-to-moderate hypertension.