Lercanidipine

Structural formula
	Structural formula without stereochemistry
General
Non-proprietary name	Lercanidipine
other names	Methyl-1,1-dimethyl-2- ( N - (3,3-diphenylpropyl) - N -methylamino) ethyl-2,6-dimethyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3,5 -dicarboxylate ( IUPAC )
Molecular formula	C 36 H 41 N 3 O 6
External identifiers / databases
ECHA InfoCard	100.235.079
PubChem	65866
DrugBank	DB00528
Wikidata	Q410492
Drug information
ATC code	C08 CA13
Drug class	Calcium antagonist
properties
Molar mass	611.73 g · mol -1
Melting point	186-190 ° C ; 119–123 ° C (lercanidipine monohydrochloride) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 301
	P: 301 + 310
Toxicological data	83 mg kg −1 ( LD 50 , mouse , ip , monohydrochloride)
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lercanidipine is a drug from the group of calcium antagonists of the dihydropyridine type. As a representative of the third generation, it is characterized by an increased vascular effect, better tolerability and also by some improved pharmacokinetic properties compared to the representatives of the second generation (including amlodipine ) . A specific pharmacokinetic disadvantage of the substance, however, is that the extent of its absorption depends on whether a meal was eaten with the tablet. A sufficiently long interval between taking medication and meals must be observed.

pharmacology

Mode of action

Lercanidipine blocks the opening of voltage-dependent calcium channels (L-type) in the smooth muscle cells of the arteries and has a high vascular specificity, which results in vasodilatation without affecting cardiac function. Due to its highly lipophilic properties, lercanidipine accumulates in the cell membrane and forms a depot there. As a result, lercanidipine is able to block the calcium channels via a membrane kinetics controlled effect despite a short plasma half-life, regardless of the plasma level .

Analytics

The reliable qualitative and quantitative determination of the active ingredient lercanidipine is required for pharmacokinetic and therapy or stability studies. After suitable sample preparation of the test material, the analysis can be carried out by using the coupling of chromatographic separation processes with mass spectrometry

Application areas (indications)

Lercanidipine is approved in Germany for the treatment of mild to moderate essential hypertension .

Contraindications (contraindications)

Lercanidipine should not be taken during pregnancy and breastfeeding, with severe kidney or liver dysfunction, unstable angina pectoris , within one month after a myocardial infarction , untreated heart failure and in conjunction with ciclosporin . Lercanidipine is also considered unsuitable for children and adolescents under 18 years of age.

Lercanidipine must not be taken if one of the following drugs / luxury foods is taken at the same time: So-called strong CYP-3A4 inhibitors (e.g. ketoconazole, itraconazole, erythromycin, troleandomycin, ritonavir), ciclosporin, grapefruit juice.

Side effects

Overall, lercanidipine appears to be well tolerated. Lercanidipine does not appear to have any negative effects on blood sugar or serum lipid levels. The symptoms typical of calcium channel blockers such as peripheral edema , headache , facial flushing, palpitations (palpitations), tachycardia , but with a significantly lower frequency than for other calcium channel blockers, were undesirable side effects .

Description of side effects by frequency :

Uncommon: accelerated heartbeat (tachycardia), palpitations, peripheral edema (fluid accumulation in the tissue, especially in the legs), headache, dizziness , feeling hot (with reddening of the skin, especially on the face).
Rare: angina pectoris (chest pain); some medicines that work similarly to lercanidipine may cause precordial pain (pain around the heart); Sleepiness ( somnolence ); Nausea; Indigestion; Diarrhea; Stomach pain; Vomiting ; increased amount of urine ( polyuria ); Nocturia ; Skin rash; Muscle aches; Weakness; Tiredness (fatigue).
Very rare: With angina pectoris, symptoms may appear more frequently or for a longer period of time or they may get worse, in isolated cases a heart attack (heart attack) may occur, fainting (syncope), increase in liver values (usually regresses after treatment is stopped), frequent urination ( Pollakiuria), hypotension (low blood pressure), chest pain, hypersensitivity.

Stereochemistry

Lercanidipine contains a stereocenter and consists of two enantiomers. This is a racemate , i.e. a 1: 1 mixture of ( R ) - and ( S ) -form:

Enantiomers of Lercanidipine
CAS number: 185197-70-0	CAS number: 185197-71-1

Trade names

Monopreparations

Carmen (D), Corifeo (D), Zanidip (A, CH), Lercanidipine generics

Combination preparations

in combination with enalapril : Carmen ACE (D), Lercaprel (A), Zaneril (D), Zanipress (D, CH), Zanipril (A)

Individual evidence

↑ ^a ^b ^c Entry on lercanidipine. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.
↑ ^a ^b data sheet Lercanidipine hydrochloride hemihydrate from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
↑ C. Álvarez, E. Gómez, M. Simón, C. Govantes, P. Guerra, J. Frías et al .: Differences in lercanidipine systemic exposure when administered according to labeling: in fasting state and 15 minutes before food intake . In: Eur J Clin Pharmacol . tape 68 , no. 7 , 2012, p. 1043-1047 , doi : 10.1007 / s00228-012-1215-8 , PMID 22294059 .
↑ K. Chen, J. Zhang, S. Liu, D. Zhang, Y. Teng, C. Wei, B. Wang, X. Liu, G. Yuan, R. Zhang, W. Zhao, R. Guo: Simultaneous determination of lercanidipine, benazepril and benazeprilat in plasma by LC-MS / MS and its application to a toxicokinetics study. In: J Chromatogr B Analyt Technol Biomed Life Sci. 899, Jun 15, 2012, pp. 1-7, PMID 22622066
↑ J. Fiori, R. Gotti, C. Bertucci, V. Cavrini: Investigation on the photochemical stability of lercanidipine and its determination in tablets by HPLC-UV and LC-ESI-MS / MS. In: J Pharm Biomed Anal. 41 (1), Apr 11, 2006, pp. 176-181. PMID 16378707
↑ ^a ^b Instructions for use for lercanidipine HCl , from Stada Arzneimittel AG, Stadastraße 2–18, 61118 Bad Vilbel (12/2009).
↑ K. Makarounas-Kirchmann, S. Glover-Koudounas, P. Ferrari: Results of a meta-analysis comparing the tolerability of lercanidipine and other dihydropyridine calcium channel blockers . In: Clin Ther . tape 31 , no. 8 , August 2009, p. 1652-1663 , doi : 10.1016 / j.clinthera.2009.08.010 , PMID 19808126 .
^ A. Schattner: Lercanidipine-associated nocturia. In: QJ Med. 104, 2011, p. 463. PMID 21349908
↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) . Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10-9 , p. 171.

[RÖMPP_Online-1] Entry on lercanidipine. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.

[Sigma-2] ta sheet Lercanidipine hydrochloride hemihydrate from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).

[pmid22294059-3] C. Álvarez, E. Gómez, M. Simón, C. Govantes, P. Guerra, J. Frías et al .: Differences in lercanidipine systemic exposure when administered according to labeling: in fasting state and 15 minutes before food intake . In: Eur J Clin Pharmacol . tape 68 , no. 7 , 2012, p. 1043-1047 , doi : 10.1007 / s00228-012-1215-8 , PMID 22294059 .

[4] K. Chen, J. Zhang, S. Liu, D. Zhang, Y. Teng, C. Wei, B. Wang, X. Liu, G. Yuan, R. Zhang, W. Zhao, R. Guo: Simultaneous determination of lercanidipine, benazepril and benazeprilat in plasma by LC-MS / MS and its application to a toxicokinetics study. In: J Chromatogr B Analyt Technol Biomed Life Sci. 899, Jun 15, 2012, pp. 1-7, PMID 22622066

[5] J. Fiori, R. Gotti, C. Bertucci, V. Cavrini: Investigation on the photochemical stability of lercanidipine and its determination in tablets by HPLC-UV and LC-ESI-MS / MS. In: J Pharm Biomed Anal. 41 (1), Apr 11, 2006, pp. 176-181. PMID 16378707

[stada-6] Instructions for use for lercanidipine HCl , from Stada Arzneimittel AG, Stadastraße 2–18, 61118 Bad Vilbel (12/2009).

[pmid19808126-7] K. Makarounas-Kirchmann, S. Glover-Koudounas, P. Ferrari: Results of a meta-analysis comparing the tolerability of lercanidipine and other dihydropyridine calcium channel blockers . In: Clin Ther . tape 31 , no. 8 , August 2009, p. 1652-1663 , doi : 10.1016 / j.clinthera.2009.08.010 , PMID 19808126 .

[8] A. Schattner: Lercanidipine-associated nocturia. In: QJ Med. 104, 2011, p. 463. PMID 21349908

[Rote_Liste-9] Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) . Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10-9 , p. 171.