Autoradiographic Studies on the Distribution of Quaternary Ammonium Compounds. III. Distribution, Excretion and Metabolism of ¹⁴C-Labeled Pancuronium Bromide in Rats

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The distribution, excretion and metabolism of ¹⁴C-labeled pancuronium bromide following intraperitoneal administration to rats were investigated by means of wholebody autoradiography and radioassay. The distribution of dimethyl-d-tubocurarine-¹⁴C iodide was also investigated in mice for comparison. Pancuronium-¹⁴C bromide was found to be accumulated rapidly in the liver, kidney and cartilage tissues such as the sternum, vertebra and trachea and slowly in the bone marrow and spleen, while no accumulation was observed in the muscular tissues and central nervous system. The accumulation in the liver continued for a long period and almost disappeared after 30 days survival. Counting of the liver radioactivity revealed that approximately 8, 2.5, 1.2 and 0.5% of the dose remained in the liver after 1, 6, 20 and 30 days, respectively ; the concentration decreased with half-life of about 11.2 days after an initial decline with half-life of about 1.2 days. It was confirmed that pancuronium bromide is excreted mainly via urine, mostly in the unchanged form. Dimethyl-d-tubocurarine-¹⁴C iodide showed a distribution pattern similar to that of pancuronium-¹⁴C bromide. The distribution pattern of pancuronium ion was thus quite similar to that of decamethonium ion, except that the latter accumulates in the muscular tissues. This is considered to be related to the fact that decamethonium is a depolarizer at the neuromuscular junctions, while both pancuronium and d-tubocurarine is a competitive depressant. It was also indicated that the extent of accumulation of bis-onium structure in the liver is determined not by the lipophilic character of the molecule, but primarily by the distance separating the two quaternary nitrogens.