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 blo od flow produced a decrease in clearance of recombinant human tissue-t ype plasminogen activator (rt-PA). 2 The purpose of this randomized, d ouble-blind, placebo-controlled, three-way, crossover investigation wa s to determine the effect of nifedipine (20 mg orally), a compound tha t increases liver blood flow, on plasma concentrations of steady state endogenous and recombinant tissue-type plasminogen activator (t-PA an d 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% conf idence interval)) as assessed by indocyanine green (ICG, 0.5 mg kg-1 i .v. bolus injection) clearance. 4 Nifedipine did not influence the pla sma concentrations of total rt-PA antigen and activity as evaluated by the areas under the rt-PA curves from 30 min (time at which nifedipin e 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 add ition, 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 lea d to substantial changes in plasma concentrations of rt-PA.