title: Disposition of nitrendipine in patients with chronic liver diseases.
abstract: Metabolism of nitrendipine occurs principally in the liver. Therefore, an alteration of pharmacokinetics has to be discussed in patients with hepatic impairment. To evaluate steady-state plasma concentrations and pharmacokinetics, a low dose of nitrendipine (5 mg/day for 3 weeks) was administered orally to patients with different chronic liver diseases (fatty liver, n = 3; chronic hepatitis, n = 2; and cirrhosis of the liver, n = 5). Nitrendipine plasma concentrations were analyzed by using a gas-liquid chromatography procedure. Twenty-two days after beginning the study, steady-state plasma concentrations were lower than 1.0 microgram/L in one patient without liver disease and in seven patients with chronic liver diseases, in contrast to three patients with alcoholic cirrhosis (5.5, 1.3, and 2.9 micrograms/L). The maximum concentration (Cmax) was 2.3 micrograms/L in the patient without liver disease and 8.3 +/- 3.9 micrograms/L in the hepatic patients. The elimination half-life was prolonged in three of five patients with cirrhosis of the liver (35, 67, and 43 h), whereas in the other patients the half-life was in a normal range (4.2-21.3 h). The area under the concentration-time curve (AUC) was enhanced in three patients with liver cirrhosis (387, 69, and 126 h/micrograms/L); in the other seven hepatic patients, results were normal (35-49 h/micrograms/L). There were no alterations observed in any patient in blood pressure and laboratory data. Oral administration of a low dose of nitrendipine resulted in slightly enhanced steady state plasma concentrations only in patients with advanced cirrhosis of the liver. The half-life, AUC, and bioavailability also seem to be altered only in a more severe state of liver disease.
authors: Hartwald-Klinik der BfA, Bad Brückenau, F.R.G.
authors: W
authors: W
authors: Zilly
authors: K D
authors: KD
authors: Rämsch
authors: M
authors: M
authors: Gothe
mesh_terms: D000328:Adult; D001682:Biological Availability; D002849:Chromatography, Gas; D002908:Chronic Disease; D005260:Female; D006207:Half-Life; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D009568:Nitrendipine