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Abstract
1. Toxicokinetics of tert-butylbicycloortho[3H]benzoate (3H-TBOB) administered into the right atrium of rat heart can be described by the biexponential equation
ct=Ae−1.6t+Be−0.013t.
2. The fast initial phase of 3H-TBOB decline in blood (t1/2=0.5min) is due to its absorption by lungs. 3H-TBOB is then transferred into liver, the primary organ of its metabolic detoxication. The high apparent distribution volumes for 3H-TBOB (1.3 and 7.1 1/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 3H-TBOB administered into the stomach is absorbed within 3 min into the circulatory system.
4. Intra-arterially administered 3H-TBOB distributes in the brain in a lateral and regional pattern.
5. Two types of 3H-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.