Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. II: Pharmacodynamics.
This study determined the kinetics of the effects of atropine on heart rate and saliva flow in three healthy male volunteers after intravenous administration of 1.35 and 2.15 mg of the drug. The pharmacokinetics of atropine and its primary metabolite, tropine, were determined simultaneously. Both the pharmacokinetic and effect data were fitted to an integrated kinetic-dynamic model. The maximum heart rate and minimum saliva flow occurred with a significant delay of 7-8 min after drug administration. Both effects were nonlinearly related to the amount of drug in the peripheral compartment. Maximum heart rates of 192 and 217% of the control values were observed at the lower and higher dose levels, respectively. Minimum saliva flows of 8 and 3% of the control values were measured after the lower and higher doses of atropine, respectively. The time durations of the positive chronotropic effect of the drug were 170 and 250 min at the lower and higher dose levels, respectively; the corresponding values for the length of the antisialogogue effect of the drug were 230 and 340 min, respectively.
D000042:Absorption; D000328:Adult; D001285:Atropine / Q000378:metabolism / Q000494:pharmacology*; D003201:Computers; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007273:Injections, Intramuscular; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D012472:Salivation / Q000187:drug effects
D001285:Atropine