Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration

The pharmacokinetics and hemodynamic effects of nifedipine were studied in patients with liver cirrhosis and in age-matched healthy control subjects. In a randomized order each subject received nifedipine by intravenous infusion (4.5 mg in 45 minutes) and as a tablet (20 mg). After intravenous nifedipine patients had a longer elimination t½ (420 ± 254 vs. 111 ± 22 minutes; P < 0.01), a greater volume of distribution (1.29 ± 0.60 vs. 0.97 ± 0.42 L/kg), and a lower systemic clearance (233 ± 109 vs. 588 ± 140 ml/min; P < 0.001). Plasma protein binding of nifedipine was lower in the patients (P < 0.001). After oral nifedipine systemic availability was much higher in patients (90.5% ± 26.2% vs. 51.1% ± 17.1%; P < 0.01) and maximal in patients with a portacaval shunt. Blood pressure decreased and heart rate increased after intravenous nifedipine and these effects could be fitted to plasma concentrations by a sigmoidal model. Maximal effects on heart rate and diastolic blood pressure were not different in liver cirrhosis. When free drug levels were considered, the concentrations corresponding to half the maximal effect were also not different. Blood pressure changes with oral nifedipine were comparable with those after intravenous infusion. We conclude that in patients with liver cirrhosis the pharmacokinetics of nifedipine are considerably altered; dose reduction is recommended when such patients need oral nifedipine. Clinical Pharmacology and Therapeutics (1986) 40, 21–28; doi:10.1038/clpt.1986.134