TERT-BUTYLBICYCLOORTHO[H-3]BENZOATE (H-3-TBOB) TOXICOKINETICS AND DISPOSITION IN RATS

1. Toxicokinetics of tert-butylbicycloortho[H-3]benzoate (H-3-TBOB) administered into the right atrium of rat heart can be described by the biexponential equation: c(t) = Ae-1.6t + Be-0.013t. 2. The fast initial phase of H-3-TBOB decline in blood (t1/2 = 0.5 min) is due to its absorption by lungs. H-3-TBOB is then transferred into liver, the primary organ of its metabolic detoxication. The high apparent distribution volumes for H-3-TBOB (1.3 and 7.1 l/kg for the initial and the terminal phase, respectively) are probably due to its lipophilicity and partitioning into lipoid tissue membranes. 3. Acid-labile TBOB is not completely hydrolysed in gastric fluid. A portion of H-3-TBOB administered into the stomach is absorbed within 3 min into the circulatory system. 4. Intra-arterially administered H-3-TBOB distributes in the brain in a lateral and regional pattern. 5. Two types of H-3-TBOB metabolites are excreted in urine and faeces. Both are more polar than the parent compound. The major components of the fraction were tentatively identified as hippuric and benzoic acid.