Simultaneous monitoring of bemoradan pharmacokinetics and hemodynamics in mongrel dogs

Biopharm Drug Dispos. 1992 Oct;13(7):539-47. doi: 10.1002/bdd.2510130707.

Abstract

This study was designed to determine the relationship between the hemodynamic responses to bemoradan, a novel cardiotonic agent, and its plasma levels after single administration of an oral dose or a 15 minute i.v. infusion to mongrel dogs, and to demonstrate that the clinical capsule formulation of bemoradan elicits a pharmacological response in the dog. Four conscious, instrumented mongrel dogs received each of four bemoradan treatments (30 micrograms kg-1 i.v., 100 micrograms kg-1 i.v., 100 micrograms kg-1 suspension p.o., or 1 mg capsule p.o.) in a Latin square cross-over design. Plasma levels of bemoradan up to 24 h post-dosing were determined by HPLC. Cardiac contractility (dP/dt), heart rate, and arterial blood pressure were continuously monitored for 8 h and again at 24 h. Results of the study indicate that there was a significant correlation between bemoradan plasma levels and dP/dt. The 1 mg clinical capsule formulation was well absorbed when compared to an oral suspension and an i.v. dose. Peak increases in dP/dt of 64 per cent at 15 min for the suspension and 53 per cent at 1 h for the capsule were observed.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Benzoxazines
  • Blood Pressure / drug effects
  • Capsules
  • Cardiotonic Agents / blood
  • Cardiotonic Agents / pharmacokinetics*
  • Cardiotonic Agents / pharmacology*
  • Chemistry, Pharmaceutical
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Infusions, Intravenous
  • Male
  • Monitoring, Physiologic
  • Myocardial Contraction / drug effects
  • Oxazines / blood
  • Oxazines / pharmacokinetics*
  • Oxazines / pharmacology*
  • Pyridazines / blood
  • Pyridazines / pharmacokinetics*
  • Pyridazines / pharmacology*

Substances

  • Benzoxazines
  • Capsules
  • Cardiotonic Agents
  • Oxazines
  • Pyridazines
  • bemoradan