The Absorption of Bretylium and Related Quaternary Ammonium Salts from the Alimentary Tract

N-Methyl-14C-labelled bretylium was injected into the lumen of segments of the gastrointestinal tract of cats prepared so that blood draining from these segments could be collected for analysis. The drug was not absorbed from the stomach. The concentration of drug in the venous blood from the duodenum rose steadily during 1.5–2 hr. but then declined to a value slightly exceeding that in the systemic blood. The greater part of the dose was not absorbed. Bretylium slowly traversed rat duodenum (mucosa to serosa) in vitro and the rate was not affected by factors that can influence carbohydrate metabolism. Transfer proceeded equally well from serosa to mucosa. To investigate means of obtaining better absorption of quaternary ammonium anti-adrenergic drugs a close analogue of bretylium bearing a choline residue was phosphorylated to give a phosphoric ester betaine (III). This was about twice as active by the oral route in cats as the parent drug, in which form it was excreted in the urine.