Interaction study between nifedipine and recombinant tissue-type plasminogen activator in healthy subjects.
1. In a previous study it was demonstrated that a decrease in liver blood flow produced a decrease in clearance of recombinant human tissue-type plasminogen activator (rt-PA). 2. The purpose of this randomized, double-blind, placebo-controlled, three-way, cross-over investigation was to determine the effect of nifedipine (20 mg orally), a compound that increases liver blood flow, on plasma concentrations of steady state endogenous and recombinant tissue-type plasminogen activator (t-PA and rt-PA) (35 mg of rt-PA over 2 h) in nine healthy male volunteers. 3. Nifedipine increased liver blood flow by 95% (42-167%) (mean (95% confidence interval)) as assessed by indocyanine green (ICG, 0.5 mg kg-1 i.v. bolus injection) clearance. 4. Nifedipine did not influence the plasma concentrations of total rt-PA antigen and activity as evaluated by the areas under the rt-PA curves from 30 min (time at which nifedipine was ingested) to 90 min during the rt-PA infusion (P > 0.05) and by analysis of a possible treatment x time interaction (P > 0.05). In addition, the plasma concentrations of endogenous t-PA remained unchanged when nifedipine was given alone. 5. In conclusion, by using nifedipine as a model compound it was demonstrated that the combination of rt-PA and a compound which increases liver blood flow probably does not lead to substantial changes in plasma concentrations of rt-PA.
Centre for Human Drug Research, Leiden, The Netherlands.
A
A
De Boer
C
C
Kluft
F J
FJ
Kasper
J M
JM
Kroon
H C
HC
Schoemaker
D D
DD
Breimer
P A
PA
Soons
A F
AF
Cohen
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D007700:Kinetics; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D009543:Nifedipine; D007208:Indocyanine Green