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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 t1/2 (420 +/- 254 vs. 111 +/- 22 minutes; P less than 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 less than 0.001). Plasma protein binding of nifedipine was lower in the patients (P less than 0.001). After oral nifedipine systemic availability was much higher in patients (90.5% +/- 26.2% vs. 51.1% +/- 17.1%; P less than 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.
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1988,
European journal of clinical pharmacology,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1978,
Verhandlungen der Deutschen Gesellschaft fur Innere Medizin,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1992,
Gastroenterology,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1990,
Revista de medicina interna, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicina interna,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
November 1979,
Clinical pharmacology and therapeutics,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1983,
Zeitschrift fur Kardiologie,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
October 1979,
The American journal of cardiology,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
May 1996,
Journal of the Medical Association of Thailand = Chotmaihet thangphaet,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
January 1981,
Archives des maladies du coeur et des vaisseaux,
C H Kleinbloesem, and
J van Harten, and
J P Wilson, and
M Danhof, and
P van Brummelen, and
D D Breimer
February 1985,
Anasthesie, Intensivtherapie, Notfallmedizin,
