Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist.
Using some calcium channel blockers of the dihydropyridine-type (amlodipine (CAS 88150-42-9, felodipine (CAS 72508-76-3), lercanidipine (CAS 100472-26-7), nifedipine (CAS 21829-25-4), nitrendipine (CAS 39562-70-4)) as example the interaction potential of these substances will be compared in terms of affecting metabolism and transport of drugs. The cytochrome P450 (CYP) isoform CYP3A4 and the P-glycoprotein (P-gp), respectively, will have a high impact for both pharmacokinetic processes, as all 5 calcium channel blockers are substrates of CYP3A4 and in addition nifedipine, nitrendipine and felodipine represent inhibitors of P-gp, which can cause an increase in the plasma levels of digoxin (model substrate of P-gp). If inducers (e.g. rifampicin, anticonvulsants, St John's wort) or inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin, nefazodone, fluvoxamine, fluoxetine, sertraline, ritonavir, indinavir, amprenavir, saquinavir or grapefruit juice) of CYP3A4 are concomitantly administered pharmacokinetic interactions could be expected to a variable extent. Some alternative drugs are mentioned which will not affect CYP3A4. In addition to these putative pharmacokinetic interactions also pharmacodynamic interactions with other cardiovascular active substances might be considered and some caution should be exercised if vasodilators are given as comedication.
Klotz
Ulrich
U
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. ulrich.klotz@ikp-stuttgart.de
D000818:Animals; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004095:Dihydropyridines / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; C060343:lercanidipine