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The influence of coadministration on digoxin and azimilide pharmacokinetics/pharmacodynamics was assessed in a randomized, 3-way crossover study in 18 healthy men. Serial blood and urine samples were obtained for azimilide and digoxin quantitation. Treatment effects on pharmacokinetics were assessed using analysis of variance. The relationship between azimilide blood concentrations and QTc prolongation was characterized by an Emax model. Effects of coadministration on pharmacodynamics were assessed using a mechanistic-based inhibition model. Azimilide pharmacokinetics was unaffected by digoxin, except for a 36% increase in CLT (P = .0325), with no change in CLo. Digoxin pharmacokinetics was unaffected by azimilide, except for a 21 % increase in Cmax (P = .0176) and a 10% increase in AUCτ (P = .0121). Digoxin coadministration increased the apparent EC50 with no effect on Emax, consistent with competitive inhibition (Ki = 0.899 ng/mL). The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important.