Binding of Barbiturates to Cytochrome

Basak used several TIs to correlate the binding of barbiturates to cytochrome 

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Basak, S.C. (1988). Binding of Barbiturates to Cytochrome P450 A QSAR Study Using log P and Topological Indices. Med.Sci.Res., 16, 281-282. 

Shaw, G.C. and A.J. Fulco (1993). Inhibition by barbiturates of the binding of Bm3Rl repressor to its operator site on the barbiturate-inducible cytochrome P450BM-3 gene of Bacillus megaterium. J.Biol. Chem. 268, 2997-3004. 

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

J-S He, AJ Fulco. A barbiturate-regulated protein binding to a common sequence in the cytochrome P450 genes of rodents and bacteria. J Biol Chem 266 7864-7869, 1991. 

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