Disposition of pranolium chloride in small mammals

1. The disposition of [14C]pranolium chloride, a dimethyl quaternary derivative of propranolol, has been studied in rats, mice and hamsters after oral or parenteral dosage.2. Elimination of 14C occurred largely via the kidneys after parenteral dosage, but biliary excretion was significant. Pranolium chloride was excreted unchanged and as a conjugate, and was also metabolized to 1-naphthol which was conjugated.3. The radiolabel was localized in the liver, kidneys, heart, lungs and gastro-intestinal tract of the rat, but did not pass the placental or blood-brain barriers to any appreciable extent. Unchanged pranolium chloride was localized in rat cardiac tissue for at least 6 h after i.v. dosage.4. Pranolium chloride was poorly and variably absorbed from the gastro-intestinal tract, of animals. Peak plasma levels occurred between 10 min and 1 h. The absorption of the pranolium cation was marginally increased after prolonged fasting, but was not affected by the presence of alternative anions.