The influence of nifedipine and captopril on liver blood flow in healthy subjects.
OBJECTIVE
Application of single methods to assess liver blood flow (LBF) yielded conflicting results on the magnitude and duration of effect on LBF of oral nifedipine and captopril. The aim of this study was to investigate the influence of these drugs on LBF by simultaneous use of ICG infusion and echo-Doppler.


METHODS
The study was performed according to a double-blind, placebo-controlled, randomized, cross-over design in nine healthy male volunteers. After an overnight fast and an equilibration period, subjects received a continuous i.v. indocyanine green (ICG) infusion for 4 h. At presumed ICG steady state (t=45 min), subjects were dosed with oral nifedipine (20 mg), captopril (50 mg) or placebo. During the experiment, blood sampling for ICG assay and measurement of portal venous blood flow (echo-Doppler) took place regularly. Treatments were compared using analysis of variance. Differences are reported with 95% confidence intervals (CI).


RESULTS
The area under the curves (AUC) for ICG over 1 h and over 3 h after nifedipine were 15% (difference in AUC: + 0.6, + 7.0 mg l(-1) min) and 22% (+ 7.0, + 28.4 mg l(-1) min) lower compared with placebo. After captopril, the AUC values were 8-10% lower compared with placebo but the 95% CIs included zero. Portal venous flow was 15% (+ 5, + 86 ml min(-1)) higher compared to placebo after nifedipine but not after captopril (-3%; -49, +33 ml min(-1)). The duration of effect on liver blood flow lasted approximately 2 h but was variable (range: 40-160 min). The time to maximal blood flow increase and the duration of effect after nifedipine were very similar for both measures of LBF. Changes in ICG concentrations could be reasonably well predicted from the changes in portal blood flow.


CONCLUSIONS
Nifedipine increases LBF for a substantial period of time but the effect is variable between subjects. This effect could be detected by both the ICG method and echo-Doppler and the findings of both methods were in agreement. In this respect it is likely that captopril does not influence LBF in healthy volunteers as no effect was detected with either method.
Burggraaf
J
J
Centre for Human Drug Research, Leiden, The Netherlands.
Schoemaker
R C
RC
Kroon
J M
JM
Cohen
A F
AF
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004396:Coloring Agents; D002216:Captopril; D009543:Nifedipine; D007208:Indocyanine Green