ABSORPTION AND DISPOSITION OF A NEW ANTIARRHYTHMIC AGENT BIDISOMIDE IN MAN

Absorption and disposition of bidisomide were studied in 12 healthy ma le subjects after a 20-min iv (1 mg/kg; N = 6) infusion and oral (2 mg /kg; N = 6) administration of the C-14-labeled drug. The oral absorpti on profile of unlabeled bidisomide was also studied after administrati on of a solution by a nasoenteric tube to different sites of the gastr ointestinal tract (stomach, duodenum, jejunum, and ileum). The systemi c availability was 61%. Absorption was slow initially and then rapid, achieving peak plasma concentrations between 2 and 4 hr. Less than com plete systemic availability was attributed to incomplete absorption ra ther than first-pass metabolism. When the drug solution was delivered directly to the stomach, two distinct peak plasma levels were found. T his was attributed to the more rapid absorption of bidisomide in the d uodenum and ileum (and/or possibly colon). Following an iv dose, plasm a levels of the drug declined with mean half-lives of 0.11, 2.0, and 1 2 hr for alpha, beta, and gamma phases, respectively, and a plasma cle arance of 380 mL/min. The percentages of the dose recovered as bidisom ide in urine and feces were 19 +/- 1 and 29 +/- 4 for the iv dose and 9.1 +/- 0.9 and 48 +/- 5 for the oral dose. Bidisomide did not exhibit substantial enantioselective pharmacokinetics in plasma regardless of the route of administration. The mean urinary excretion of the (-) en antiomer was, however, slightly higher than that of the (+) enantiomer , with (-)/(+) enantiomeric ratios of 1.2 and 1.3 after iv and oral ad ministration, respectively. The enantiomeric ratio of bidisomide recov ered in the feces was approximately 1.