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The reactivity of the nitroso metabolites of these drugs with GSH and/or proteins in target organs has also been demonstrated.55,56 Genetic polymorphisms in glutathione-S-transferase (GST) isozymes, which catalyze GSH conjugation to reactive metabolites, are also considered risk factors for hepatotoxicity caused by several drugs such as troglitazone and carbamazepine.57,85 It is possible that patients deficient in GST isozymes are most at risk towards liver injury by reactive metabolites of troglitazone and carbamazepine because of ineffective scavenging of the reactive metabolites derived from the oxidative bioactivation of these drugs

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These data support the intuitive need for higher oral doses or repeated administration, but they do not establish therapeutic exposure targets for any disease