THE BIOLOGIC DISPOSITION OF PENTAZOCINE IN THE RAT

¹ Department of Pharmacology, School of Medicine, University of California, San Francisco, California

The absorption, distribution, excretion and metabolism of pentazocine were studied by a spectrophotofluorometric procedure. Oral absorption of pentazocine was rapid as evidenced by its rate of disappearance from the gastro-intestinal tract and appearance in blood and in tissues. Levels of the drug were low, however, due to rapid inactivation by the liver. After i.v. administration, pentazocine was rapidly taken up by parenchymatous tissue and was found in high concentrations in the lung, spleen, kidney and also the brain. Liver levels were high at one minute but barely detectable at 15 minutes, whereas appreciable levels were still noted in other organs for at least two hours. Very little unchanged pentazocine was excreted in urine and feces; less than 10% of the drug was accounted for as extractable fluorescent products and counter-current distribution of this material revealed that only a minor fraction could be attributed to pentazocine. The chief biotransformation products are conjugates of glucuronic acid which appear early in the bile and urine. Small amounts of pentazocine can be accounted for in urine as conjugated sulfates and as nonconjugated phenolic metabolites. No evidence for N-dealkylation of the drug to norpentazocine was obtained. Rapid and extensive metabolism of pentazocine was effected by the liver homogenate and the presence of calcium in the medium markedly inhibited the reaction.