Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls

Int J Clin Pharmacol Ther. 1998 Jul;36(7):386-91.

Abstract

The pharmacokinetics and safety of a single oral dose of 20 mg manidipine dihydrochloride have been studied in 8 patients with mild to moderate hepatic impairment (grade A or B in Child's classification, or score < or = 7 in Pugh's modification of Child's classification), and in 12 healthy subjects. They received one 20 mg manidipine dihydrochloride tablet with 100 ml of tap water after a standard breakfast. Manidipine was determined using HPLC with electrochemical detection from plasma samples taken up to 24 or 36 h after dosing. The medication was well tolerated. A trend toward higher Cmax, AUC, and MRT was observed in patients with a more severe hepatic impairment, as a consequence of reduction in the liver metabolic function. Patients with grade A hepatic impairment did not exhibit significantly altered pharmacokinetics with respect to healthy subjects, while grade B impairment patients had significantly higher AUC and MRT. Tmax values pointed to reduced absorption rate in patients compared to healthy subjects; the changes were more evident in grade B than grade A patients, although statistical significance was not reached. The reduction in absorption rate in grade B patients is probably related to their higher mean age, since this effect has been reported for manidipine. The pharmacokinetics of manidipine seem only modified in patients with a certain degree of hepatic impairment (at least Pugh grade 6 and Child grade B); therefore, adaptation of the dosing regimen does not seem to be generally recommendable, but should be modulated according to the liver status of the patient.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / blood
  • Antihypertensive Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Dihydropyridines / administration & dosage
  • Dihydropyridines / blood
  • Dihydropyridines / pharmacokinetics*
  • Half-Life
  • Humans
  • Liver Cirrhosis, Alcoholic / classification
  • Liver Cirrhosis, Alcoholic / metabolism*
  • Male
  • Middle Aged
  • Nitrobenzenes
  • Piperazines
  • Reference Values
  • Severity of Illness Index

Substances

  • Antihypertensive Agents
  • Dihydropyridines
  • Nitrobenzenes
  • Piperazines
  • manidipine