title: Simultaneous monitoring of bemoradan pharmacokinetics and hemodynamics in mongrel dogs.
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.
authors: R. W. Johnson Pharmaceutical Research Institute at Ortho Pharmaceutical Corporation, Raritan, NJ 08869.
authors: S M
authors: SM
authors: Huang
authors: R
authors: R
authors: Falotico
authors: B
authors: B
authors: Haertlein
authors: I L
authors: IL
authors: Smith
mesh_terms: D000284:Administration, Oral; D000818:Animals; D048588:Benzoxazines; D001794:Blood Pressure / Q000187:drug effects; D002214:Capsules; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D008991:Monitoring, Physiologic; D009200:Myocardial Contraction / Q000187:drug effects; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011724:Pyridazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D048588:Benzoxazines; D002214:Capsules; D002316:Cardiotonic Agents; D010078:Oxazines; D011724:Pyridazines; C062457:bemoradan