Lercanidipine

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Lercanidipine
Clinical data
Trade namesZanidip, Leridip
AHFS/Drugs.comUK Drug Information
Pregnancy
category
  • C (no data in humans)
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
first-pass effect)
Protein binding>98%
MetabolismMainly CYP3A4
Elimination half-life8–10 hours
Duration of action≥ 24 hours
ExcretionUrine (50%)
Identifiers
  • (RS)-2[(3,3-Diphenylpropyl)(methyl)amino]-1,1-dimethylethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
JSmol)
  • [O-][N+](=O)c1cccc(c1)C4C(=C(/N\C(=C4\C(=O)OC(C)(C)CN(CCC(c2ccccc2)c3ccccc3)C)C)C)\C(=O)OC
  • InChI=1S/C36H41N3O6/c1-24-31(34(40)44-6)33(28-18-13-19-29(22-28)39(42)43)32(25(2)37-24)35(41)45-36(3,4)23-38(5)21-20-30(26-14-9-7-10-15-26)27-16-11-8-12-17-27/h7-19,22,30,33,37H,20-21,23H2,1-6H3 checkY
  • Key:ZDXUKAKRHYTAKV-UHFFFAOYSA-N checkY
  (verify)

Lercanidipine (trade name Zanidip, among others) is an

dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.[1]

The drug acts more slowly than older dihydropyridines.[citation needed] It probably has fewer adverse effects, but a comparatively high potential for drug interactions.

It was patented in 1984 and first approved for medical use in 1997.

US FDA refused to approve the drug, and lercanidipine is not marketed in USA.[3]

Medical uses

Lercanidipine is used for the treatment of essential hypertension (high blood pressure).[4][5]

Lercanidipine seems to be a good agent in treating hypertensive patients that also have kidney issues.[6]

Contraindications

Like other dihydropyridines, lercanidipine is contraindicated in unstable

renal impairment.[4][5]

The drug must not be combined with strong inhibitors of the liver enzyme CYP3A4 or with the immunosuppressant drug ciclosporin.[4][5]

Adverse effects

Lercanidipine is generally well tolerated; no single adverse effect has been observed in more than 1% of patients treated with this drug. Typical side effects are similar to those of other drugs of this class and include headache, dizziness,

oedema. Hypersensitivity reactions occur in less than one patient in 10,000.[4][5]

Oedemas are significantly less common under lercanidipine when compared to first-generation dihydropyridines such as nifedipine. For other side effects, data are inconclusive: A study comparing lercanidipine to first-generation drugs found no difference in the frequency of headache and flush,[7] but switching from amlodipine, felodipine or nitrendipine (all at least second generation) to lercanidipine significantly decreased side effects in another study.[5]

Overdose

Overdosing of up to 80 times the usual therapeutic dose has been described. Expected symptoms include severe

lipid membranes of cells.[4]

Interactions

The substance is metabolised by the liver enzyme CYP3A4. In a study, the strong CYP3A4 inhibitor

St John's wort probably lower plasma levels and effectiveness of lercanidipine.[5][8] By comparison, amlodipine has a lower potential for CYP3A4 mediated interactions.[4][9]

Lercanidipine increases plasma levels of ciclosporin and digoxin.[4][5]

Pharmacology

Mechanism of action

Like other dihydropyridine class calcium channel blockers, lercanidipine blocks L-type calcium channels in the smooth muscle cells of blood vessels, relaxing them and thus lowering blood pressure. In contrast to the non-dihydropyridine calcium channel blockers verapamil and diltiazem, it does not significantly act on calcium channels in the atrioventricular node, and therefore does not decrease heart rate, in usual therapeutic doses.[5]

Pharmacokinetics

Lercanidipine is slowly but completely absorbed from the gut. It has a total

first-pass effect, or up to 40% if taken after a fatty meal. Highest blood plasma levels are reached after 1.5 to 3 hours. The substance is quickly distributed into the tissues and bound to lipid membranes, where it forms a depot. The circulating fraction is almost completely (>98%) bound to plasma proteins.[4][5]

It is completely metabolized in the liver, mainly via CYP3A4.

Elimination half-life is 8 to 10 hours, and the drug does not accumulate. Because of the depot effect, the antihypertensive action lasts for at least 24 hours. 50% is excreted via the urine.[4][5]

Chemistry

Lercanidipine is used in form of the hydrochloride,[4] which is a slightly yellow crystalline powder and melts at 197 to 201 °C (387 to 394 °F) in crystal form I or 207 to 211 °C (405 to 412 °F) in crystal form II.[10] It is readily soluble in chloroform and methanol, but practically insoluble in water.[11] This high lipophilicity (compared to older dihydropyridines) is intentional because it causes the substance to bind to lipid membranes, allowing for a longer duration of action.[12]

The lercanidipine molecule has one

racemate).[5][13]

Enantiomers of lercanidipine

(R)-lercanidipin
CAS number: 185197-70-0
(S)-lercanidipin
CAS number: 185197-71-1

Detection in body fluids

Blood plasma concentrations of lercanidipine can be detected by liquid chromatography–mass spectrometry methods.[14]

References

  1. PMID 17073834
    .
  2. ISBN 9783527607495
    .
  3. ^ "NCATS Inxight Drugs — LERCANIDIPINE HYDROCHLORIDE". drugs.ncats.io. Retrieved 2024-04-16.
  4. ^ a b c d e f g h i j k Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  5. ^
    ISBN 978-3-7741-9846-3
    .
  6. PMID 29472747
    .
  7. S2CID 42580226
    .
  8. ^
    S2CID 38892707
    .
  9. PMID 11069440
    .
  10. ^ US 6852737, Bonifacio F, Campana F, De Iasi G, Leonardi A, "Crude and crystalline forms of lercanidipine hydrochloride", issued 8 February 2005, assigned to Recordati Ireland Ltd. 
  11. ^ "Zanidip Data Sheet" (PDF). Medsafe. Retrieved 15 July 2016.
  12. ^ Gasser R, Klein W, Köppel H (January 1999). "Lercanidipine, a new third generation Ca-antagonist in the treatment of hypertension" (PDF). Journal of Clinical and Basic Cardiology. 2 (2): 169–174.
  13. ISBN 978-3-946057-10-9
    , S. 171.
  14. PMID 22622066
    .

Further reading

External links