title: Pharmacokinetic and pharmacodynamic interactions of propafenone and cimetidine.
abstract: The pharmacokinetics and pharmacodynamics of the extensively metabolized antiarrhythmic agent propafenone were assessed alone and during concomitant administration of cimetidine. Twelve healthy subjects were given successively the following treatments: propafenone 225 mg q8h plus cimetidine placebo; cimetidine 400 mg q8h plus propafenone placebo; and propafenone 225 mg plus cimetidine 400 mg q8h. After a minimum of 5 days on each regimen, plasma drug concentrations and electrocardiogram conduction intervals were measured during a drug washout period. The maximum concentration of propafenone in plasma was 993 +/- 532 ng/mL when propafenone was given alone compared with 1230 +/- 591 ng/mL when propafenone was given with cimetidine (P = .0622). Differences in tmax, t1/2, and Cp ss did not approach statistical significance when propafenone alone was compared with propafenone plus cimetidine. When compared with cimetidine, propafenone significantly increased the PR interval from 161 +/- 5 msec to 192 +/- 6 msec (P less than .01) and the QRS duration from 89 +/- 3 msec to 98 +/- 4 msec (P less than .01). Combination therapy caused a modest additional increase in QRS duration to 103 +/- 3 msec (P less than .01). In conclusion, cimetidine caused small changes in propafenone pharmacokinetics and pharmacodynamics; but these changes are unlikely to be clinically important.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: E L
authors.initials: EL
authors.lastname: Pritchett
authors.forename: W M
authors.initials: WM
authors.lastname: Smith
authors.forename: E B
authors.initials: EB
authors.lastname: Kirsten
mesh_terms: D000328:Adult; D002927:Cimetidine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D004562:Electrocardiography; D006801:Humans; D008297:Male; D011405:Propafenone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D013997:Time Factors
chemical_list: D011405:Propafenone; D002927:Cimetidine; D012083:Renin