Analysis of the thrombin inhibitor DuP 714 by an enzyme-linked immunosorbent assay

Blood Coagul Fibrinolysis. 1994 Aug;5(4):517-21.

Abstract

A competition enzyme-linked immunosorbent assay (ELISA) has been developed for the quantitative detection in plasma of DuP 714, a boroarginine tripeptide (Ac-(D)-Phe-Pro-boroArg) with potent antithrombin activity. The assay has been used to calculate the half-life after i.v. administration of DuP 714, as well as the percent bioavailability after oral administration of the agent. Following i.v. administration, in dogs, the clearance of compound from the circulation could best be fit to a biexponential decay with an initial half-life of approximately 9 min, and a slower elimination phase with a half-life of 40 min. There was a significant correlation between pharmacokinetic and pharmacodynamic characteristics (r = 0.9570, P < 0.01) as measured with the ELISA and the clotting assay, aPTT, following i.v. infusion in conscious dogs. A plasma concentration of 311 ng/ml doubled the aPTT. After oral administration of 1 mg/kg DuP 714, peak concentration ranged from 384 to 584 ng/ml. Oral bioavailability, determined by comparing the areas under concentration vs time curves after oral and i.v. administration, was 53 +/- 8% (n = 4). In summary, this assay offers a rapid, sensitive and specific method of examining the peptide's pharmacokinetic characteristics.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antithrombins / administration & dosage
  • Antithrombins / analysis*
  • Antithrombins / pharmacokinetics
  • Biological Availability
  • Boron Compounds / administration & dosage
  • Boron Compounds / analysis*
  • Boron Compounds / immunology
  • Boron Compounds / pharmacokinetics
  • Cross Reactions
  • Dogs
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Half-Life
  • Infusions, Intravenous
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oligopeptides / administration & dosage
  • Oligopeptides / analysis*
  • Oligopeptides / immunology
  • Oligopeptides / pharmacokinetics
  • Partial Thromboplastin Time
  • Thrombin / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antithrombins
  • Boron Compounds
  • Oligopeptides
  • acetylphenylalanyl-prolyl-boroarginine
  • Thrombin