Abstract
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.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bauer L. A., Stenwall M., Horn J. R., Davis R., Opheim K., Greene L. Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil, and diltiazem therapy. Clin Pharmacol Ther. 1986 Aug;40(2):239–242. doi: 10.1038/clpt.1986.169. [DOI] [PubMed] [Google Scholar]
- CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
- Feely J. Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects. Br J Clin Pharmacol. 1984 Jan;17(1):83–85. doi: 10.1111/j.1365-2125.1984.tb05003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George C. F. Drug kinetics and hepatic blood flow. Clin Pharmacokinet. 1979 Nov-Dec;4(6):433–448. doi: 10.2165/00003088-197904060-00003. [DOI] [PubMed] [Google Scholar]
- Gold H. K., Leinbach R. C., Garabedian H. D., Yasuda T., Johns J. A., Grossbard E. B., Palacios I., Collen D. Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion. Circulation. 1986 Feb;73(2):347–352. doi: 10.1161/01.cir.73.2.347. [DOI] [PubMed] [Google Scholar]
- Rappaport P. L., Thiessen J. J. High-pressure liquid chromatographic analysis of indocyanine green. J Pharm Sci. 1982 Feb;71(2):157–161. doi: 10.1002/jps.2600710205. [DOI] [PubMed] [Google Scholar]
- Smith D., Gilbert M., Owen W. G. Tissue plasminogen activator release in vivo in response to vasoactive agents. Blood. 1985 Oct;66(4):835–839. [PubMed] [Google Scholar]
- Sorkin E. M., Clissold S. P., Brogden R. N. Nifedipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs. 1985 Sep;30(3):182–274. doi: 10.2165/00003495-198530030-00002. [DOI] [PubMed] [Google Scholar]
- Stenson R. E., Constantino R. T., Harrison D. C. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation. 1971 Feb;43(2):205–211. doi: 10.1161/01.cir.43.2.205. [DOI] [PubMed] [Google Scholar]
- Verheijen J. H., Mullaart E., Chang G. T., Kluft C., Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemost. 1982 Dec 27;48(3):266–269. [PubMed] [Google Scholar]
- Zito R. A., Reid P. R. Lidocaine kinetics predicted by indocyanine green clearance. N Engl J Med. 1978 May 25;298(21):1160–1163. doi: 10.1056/NEJM197805252982102. [DOI] [PubMed] [Google Scholar]
- de Boer A., Kluft C., Kroon J. M., Kasper F. J., Schoemaker H. C., Pruis J., Breimer D. D., Soons P. A., Emeis J. J., Cohen A. F. Liver blood flow as a major determinant of the clearance of recombinant human tissue-type plasminogen activator. Thromb Haemost. 1992 Jan 23;67(1):83–87. [PubMed] [Google Scholar]
