Nisoldipine: kinetics and effects on blood pressure and heart rate in patients with liver cirrhosis after intravenous and oral administration.
The pharmacokinetics and effects on blood pressure and heart rate of nisoldipine were studied in 8 patients with cirrhosis and in 8 age-matched healthy controls. On separate occasions each subject received nisoldipine by i.v. infusion (0.37 mg in 40 min) and as a tablet (5 mg for patients and 20 mg for control subjects). After i.v. nisoldipine, the elimination half-life was 9.7 h in control subjects and 16.6 h in the cirrhotics. The volume of distribution was 4.1 l/kg and 6.4 l/kg and the total systemic clearance was 847 ml/min and 494 ml/min, respectively. On oral nisoldipine, systemic availability was fourfold higher in patients with cirrhosis: 14.7% versus 3.7%. After i.v. administration of nisoldipine there was a brief decrease in systolic and diastolic blood pressure in both groups, whereas the heart rate increased. After 4 h a second effect peak appeared in the control subjects. After oral nisoldipine similar effect-time profiles were found, but effects lasted longer than after i.v. administration. Comparison of the maximal total plasma concentration of nisoldipine and the maximal effect in the two groups revealed that sensitivity to nisoldipine was not different in patients with cirrhosis. A reduction in the dose of nisoldipine is recommended when cirrhotics require oral nisoldipine in therapeutic practice.
van Harten
J
J
Division of Pharmacology, University of Leiden, The Netherlands.
van Brummelen
P
P
Wilson
J H
JH
Lodewijks
M T
MT
Breimer
D D
DD
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D015737:Nisoldipine
D002121:Calcium Channel Blockers; D015737:Nisoldipine; D009543:Nifedipine