Nilvadipine: profile of a new calcium antagonist. An overview

J Cardiovasc Pharmacol. 1994;24 Suppl 2:S92-107.

Abstract

Nilvadipine is a new calcium antagonist of the the dihydropyridine group. Owing to its high receptor affinity, nilvadipine blocks L-type calcium channels in vascular muscle cells. This leads to prolonged vascular relaxation and lowering of blood pressure. In comparison with nifedipine, the prototype of the dihydropyridines, nilvadipine possesses special pharmacokinetic and pharmacodynamic properties. The duration of action is longer, and the vasodilatory effect is 5-16 times greater. Compared with nifedipine, the cardiodepressive action and the adrenergic counterregulation are less intense for nilvadipine. Nilvadipine's higher vasoselectivity is expressed in a vascular/cardiac efficacy quotient of 251, is 9-10 times higher than that of nifedipine. In therapeutic dosages nilvadipine has no negative inotropic, chronotropic, or dromotropic effects. In various in vitro and animal experiments, nilvadipine demonstrated a good antiatherogenic action. Nilvadipine is absorbed quickly and completely. Owing to a marked first-pass effect, the absolute bioavailability is 14-19%. The final elimination half-life is between 15 and 20 h, probably due to slow redistribution from the tissue. Nilvadipine is mainly excreted via the kidneys in the form of inactive metabolites. The pharmaceutical preparation as a depot form prevents an over-increase of the plasma level, and therefore reduces the typical side effects of dihydropyridine calcium antagonists. The pharmacokinetics of nilvadipine are not affected by reduced renal function. The bioavailability is increased in liver cirrhosis, but with repeated administration no cumulative effect takes place. Because of nilvadipine's long half-life, a once-daily administration is adequate to reduce blood pressure over 24 h in the treatment of arterial hypertension. At a daily dosage of 8-16 mg, the responder rate (RRdiast < 90 mm Hg) is 60-70% in single-drug therapy and up to 80% in combination therapy. Nilvadipine can be used to treat hypertensive patients who are also suffering from diabetes mellitus, lipometabolic disturbances, chronic obstructive respiratory tract disease, or cerebral circulatory disturbances. Owing to its high vascular selectivity, antiatherogenic properties, 24-h action, and good tolerance, nilvadipine fulfills the requirements for a modern antihypertensive agent.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Biological Availability
  • Blood Pressure / drug effects*
  • Calcium Channel Blockers / pharmacokinetics
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Cerebrovascular Circulation / drug effects
  • Dose-Response Relationship, Drug
  • Heart / drug effects
  • Humans
  • Hypertension / drug therapy
  • Lung / drug effects
  • Middle Aged
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacokinetics
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Structure-Activity Relationship
  • Vasodilation / drug effects

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • nilvadipine
  • Nifedipine