Plasma levels of a novel antidysrhythmic agent, meobentine sulfate, in humans as determined by radioimmunoassay.
A radioimmunoassay for the quantitation of meobentine sulfate, a novel antidysrhythmic and antifibrillatory agent in biological fluids, is described. Antisera were raised in rabbits in response to immunization with a conjugate of bovine serum albumin and a meobentine analog with a propionic acid sidechain ortho to the methoxyl group. These antisera have low affinities for N- and O-desmethylmeobentine metabolites, which show less than 5% cross-reaction in radioimmunoassay procedures employing either tritiated or radioiodinated radioligands. The radioimmunoassay using[125I]meobentine was capable of detecting less than 0.4 ng/ml (40-pg mass) of meobentine. This assay was used to demonstrate the absorption of meobentine in humans after oral administration and also permitted studies of meobentine sulfate disposition in human plasma following two (2.5 and 5 mg/kg) oral doses. Mean peak meobentine concentrations in plasma occurred 3 hr postdose in both cases and were 230 and 451 ng/ml following the 2.5- and 5-mg/kg doses, respectively. The approximate mean terminal half-life after all treatments was 12 hr.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D000918:Antibody Specificity; D001682:Biological Availability; D005260:Female; D006146:Guanidines / Q000097:blood*; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008760:Methylguanidine / Q000031:analogs & derivatives / Q000097:blood*; D011817:Rabbits; D011863:Radioimmunoassay / Q000379:methods
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D008760:Methylguanidine; C032896:meobentine