Reproducibility of the pharmacokinetic-hemodynamic response to nitroglycerin in the dog: a model for studying the effects of chronic treatment.
We studied six dogs to determine the hemodynamic response to and pharmacokinetics of intravenous nitroglycerin (i.v. GTN) before and after a five-day treatment with placebo ointment. On the first study day, the major hemodynamic response to 21 micrograms/min i.v. GTN was an 11.4% +/- 5.6 (S.D.) fall in systolic blood pressure (SBP) from a control of 180 mmHg +/- 16 to 158 mmHg at 21 micrograms/min i.v. GTN. This finding was reproduced (a 12.6% +/- 5.6 fall in SBP) on the second study day. On the first day, the relationship between the arterial GTN concentration and the infusion rate was linear, the arterial t1/2 for GTN was short (1.9 min +/- 0.6) and there was an 80% arterial-venous extraction for GTN; these values were unchanged by five days of treatment with placebo. We conclude that this model is a sensitive and reproducible system for studying the in vivo effects of sustained drug treatment.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D005996:Nitroglycerin