Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nilvadipine is absorbed rapidly and completely and its absolute bioavailability is about 14-19% because of its high first-pass metabolism. Maximum plasma levels and the extent of bioavailability increase proportionally with the dose. Nilvadipine is mainly excreted via the kidney as inactive metabolites. Slow tissue redistribution is probably the reason for the terminal elimination half-life of 15-20 h. There was a good correlation between the estimated tissue concentration and the reduction in blood pressure in patients. The use of the sustained-release pellet formulation can prevent plasma level peaks and thereby lessen the typical side effects of dihydropyridine calcium antagonists. The pharmacokinetics of nilvadipine were not affected by impaired renal function, and although the bioavailability was increased in liver cirrhosis, there was no accumulation after repeated doses. There was no effect on plasma digoxin levels. The plasma concentration of nilvadipine can be affected by either activation or inhibition of the cytochrome P450 system. The use of a sustained-release once-a-day formulation to lower the peaks in plasma levels along with nilvadipine's long terminal half-life means that this well-tolerated pharmaceutical formulation can be employed in clinical trials for the treatment of hypertension and expected to work over 24 h.
 ...
PMID:Pharmacokinetics of nilvadipine. 128 85

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.
 ...
PMID:Nilvadipine: profile of a new calcium antagonist. An overview. 789 1