Effect of cimetidine on quinidine bioavailability

✍ Scribed by Janis J. Mackichan; Harisios Boudoulas; Stephen F. Schaal

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 280 KB
• Volume: 10
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510100114

✦ Synopsis

Elevations in quinidine steady-state serum concentrations have been re orted in patients who received cimetidine concurrently."' Studies in normal volunteers3' have shown that areas under the serum concentration-time curve of orally administered quinidine are higher when quinidine is given during chronic cimetidine therapy as compared to under control conditions. The mechanism for this interaction is generally ascribed to decreased hepatic clearance as a consequence of enzyme inhibition. In this study, we show that cimetidine also decreases the bioavailable fraction of quinidine.

KEY WORDS Quinidine Cimetidine Bioavailability Drug interaction B METHODS Four healthy subjects (two men and two women, 25 to 31 years, weighing 53 to 84 kg) completed all phases of the study. Subjects were drug and alcohol free for at least 1 week prior to and during the study. Subjects received quinidine on four occasions separated by 1 to 2 weeks. Oral and intravenous quinidine doses were given before treatment with cimetidine and again after at least 5 days of pretreatment with cimetidine (Tagamete), 300 mg every 6 h. During experimental phases, cimetidine intake was continued during blood and urine sampling periods. Quinidine was given orally as 300 mg quinidine sulfate (Quinorao, Key Pharmaceuticals) and intravenously as 300 mg quinidine gluconate U.S.P. (Lilly). The intraveous dose was diluted to 30ml with 5 per cent dextrose in water and infused by constant rate syringe pump over 30 min; residual infusion fluid was assayed by liquid chromatography' to determine the actual dose of quinidine base. Blood samples were collected in non-heparinized glass tubes prior to each quinidine dose, and at 0.5, 1, 2, 3, 4, 5, 7, 9, and 12 h following oral administration or the end of intravenous infusion.