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Influence of Coadministration on the Pharmacokinetics of Azimilide Dihydrochloride and Digoxin
Author(s) -
Toothaker Roger D.,
Corey Alfred E.,
Valentine Suzanne N.,
Agnew Jeff R.,
Parekh Nikhil,
Moehrke Werner,
Thompson Gary A.,
Powell James H.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005276948
Subject(s) - digoxin , pharmacokinetics , medicine , pharmacology , heart failure
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 QT c prolongation was characterized by an E max 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 CL r (P = .0325), with no change in CL o . Digoxin pharmacokinetics was unaffected by azimilide, except for a 21% increase in C max (P = .0176) and a 10% increase in AUC τ (P = .0121). Digoxin coadministration increased the apparent EC 50 with no effect on E max , consistent with competitive inhibition (K i = 0.899 ng/mL). The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important.