Neuropsychologic effects of diazepam related to single dose kinetics and liver function

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Abstract
The neurophysiologic and neuropsychologic effects and their relation to the kinetics of diazepam (DZ) were studied in 10 patients with impaired liver function of various degrees and in three normal subjects after 10 mg DZ i.v. The plasma concentration data were treated according to a two-compartment open model. Neurophysiologic effect measurements were obtained from galvanic skin response, continuous reaction times (CRT), heart rate, and averaged evoked potentials; neuropsychologic measurements were obtained from trail making A+B, hidden pattern, word fluency, and subtraction tests; in addition, clinical effects were rated by Beechers Mood Scale and Spielbergers Anxiety Scale. Except for trail making A and word fluency all tests discriminated well between the experimental conditions with or without diazepam. No difference from normal in the response to acute diazepam administration could be detected in patients with reduced liver function. A linear correlation between prolongation in CRT and DZ log plasma concentration was demonstrated in the entire, heterogenous patient material. In the clinical ratings only items of a predominantly sedative and autonomic significance responded to the diazepam injection, while predominantly anxiolytic items did not.