title: The antiarrhythmic activity of meobentine sulfate in man.
abstract: Meobentine (sulfate) has antifibrillatory and antiarrhythmic activity in canine models. The antiarrhythmic, pharmacokinetic, and adrenergic neuronal blocking effects of meobentine were assessed in 15 patients with chronic, high-frequency ventricular ectopic depolarizations (VEDs). Eleven of the 15 patients had recurrent nonsustained ventricular tachycardia. The patients were given a series of gradually increasing single doses of meobentine; six received oral meobentine and nine had infusions. The antiarrhythmic efficacy of meobentine was assessed by a comparison of arrhythmia frequency during placebo given on days just prior to meobentine. Oral therapy with meobentine at dosages above 20 mg/kg caused diarrhea, and well-tolerated dosages achieved peak concentrations of 0.69 micrograms/ml (range 0.5-1.0 micrograms/ml). Antiarrhythmic activity was seen in only one patient with oral meobentine. In contrast, intravenous infusions (6.75-34.2 mg/kg) achieved concentrations ranging from 1.3-9.8 micrograms/ml. There was a linear relationship between pseudo-steady-state plasma concentrations and dosage, r = 0.82, p less than 0.01. Antiarrhythmic activity was seen in four of nine patients who received intravenous meobentine over a range of concentrations from 2.5-4.5 micrograms/ml. Four patients developed evidence of adrenergic neuronal blockage (loss of the venous reflex response); two at dosages of 16.2 mg/kg, one at 24.3 mg/kg, and one at 34.2 mg/kg. In one individual (24.3 mg/kg), the adrenergic neuronal blockade was associated with an acute episode of shortness of breath, orthopnea, and cough. With intravenous meobentine, there was a linear relationship between dosage and AUC, and the elimination half-life ranged from 11-27 h.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004341:Drug Evaluation; D004569:Electroencephalography; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008760:Methylguanidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D008760:Methylguanidine; C032896:meobentine