Interaction study between nifedipine and recombinant tissue‐type plasminogen activator in healthy subjects

• Published in: British journal of clinical pharmacology Vol. 36; no. 2; pp. 99 - 104
• Main Authors: Boer, A, Kluft, C, Kasper, FJ, Kroon, JM, Schoemaker, HC, Breimer, DD, Soons, PA, Cohen, AF
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1993; Blackwell Science
• Subjects: Adult; Biological and medical sciences; Blood Pressure - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Double-Blind Method; Drug Interactions; Heart Rate - drug effects; Humans; Indocyanine Green - metabolism; Kinetics; Liver Circulation - drug effects; Male; Medical sciences; Nifedipine - pharmacology; Pharmacology. Drug treatments; Recombinant Proteins - blood; Tissue Plasminogen Activator - blood; Human; Intravenous administration; Pyridine(dihydro) derivative; Oral administration; Drug interaction; Normal; Pharmacokinetics; Blood plasma
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.1993.tb04203.x

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.