Extravascular liver/blood and brain/blood ratios were found to be an average of 6% and 1% higher, respectively, in all experiments than total liver/blood and brain/blood ratios. This difference may be informative in establishing true tissue levels. There was a significant time effect (P less than 0.05) with the extravascular liver/blood ratios but not with the extravscular brain/blood ratios. Extravascular liver/blood ratios were slightly higher in phenobarbital-pretreated animals than in non-pretreated animals. Tissue secobarbital levels in pretreated and non-pretreated animals are not different at 1/4 or 1 h, even though pretreated animals received higher doses than non-pretreated animals. Tissue levels are significantly higher (P less than 0.01) in pretreated animals than in non-pretreated animals at 4 h. It is possible that, at this time period, the barbiturate-metabolizing enzymes have become saturated or exhausted.
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