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)