Close correlation of acetaminophen clearance with that of conjugated benzodiazepines but not oxidized benzodiazepines

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Abstract
Summary The clearance of the antipyretic-analgesic drug acetaminophen, biotransformed in humans by glucuronide and sulfate conjugation, was evaluated in 32 healthy young and elderly volunteers. Subjects received a single 650-mg dose of acetaminophen, and multiple plasma concentrations measured over the next 12 h. Random subgroups of subjects also participated in studies of the oxidized benzodiazepines diazepam, desmethyldiazepam and alprazolam, and of the conjugated benzodiazepines lorazepam, oxazepam and temazepam. Acetaminophen clearance was not related to that of the oxidized benzodiazepines, but was highly correlated with clearance of lorazepam (r=0.70, n=11, pr=0.76, n=14, pr=0.63, n=16, p<0.01). Thus acetaminophen may serve as a probe or marker compound to evaluate drug conjugating capacity in humans.

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