Pharmacodynamic modeling of digoxin-induced bradycardia

摘要: Digoxin-induced bradycardia in dogs was used to evaluate several pharmacodynamic models. Digoxin plasma concentrations and response were monitored beagle administered either 0.05 or 0.025 mg/kg of digoxin iv as an infusion over 5 min. The models investigated the linking model, linear effect compartment inhibitory model. Regression procedures for investigating model conducted with Emax (the maximal response, where percentage decrease heart rate) a variable upper bound 100%, constant value alternately equal observed reponse. Based on statistical criteria using Emax, found be best describing digoxin-induced bradycardia. For CPss(50) (concentration at steady state that will produce 50% response) ranged from 3.8–9.8 ng/ml; δ (exponent steepness concentration-response relationship) 0.6–7.1. implications these understanding concentration-effect relationships are discussed.