Skip to main content
Log in

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

  • Human Pharmacology
  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arnold, E.: A simple method for determining diazepam and its major metabolites in biological fluids: Application in biovailability studies. Acta pharmacol. (Kbh.) 36, 335–352 (1975)

    Google Scholar 

  • Beecher, H. K., Measurement of subjective responses New York: Oxford University Press 1959

    Google Scholar 

  • Berlin, A. B., Siwers, B., Agurell, S., Hiort, A., Sjöqvist, F., Ström, S. Determination of bioavailability of diazepam in various formulations from steady state plasma concentration data. Clin. Pharmacol. Ther. 13, 733–744 (1973)

    Google Scholar 

  • Bianchi, G. N., Fennessy, M. R., Philips, J., Everitt, B. S.: Plasma level of diazepam as a therapeutic predictor in anxiety states. Psychopharmacologia (Berl.) 35, 113–122 (1974)

    Google Scholar 

  • Brun, P., Parsons, O. A.: Continuous reaction times in brain damage. Cortex 7, 278–291 (1971)

    Google Scholar 

  • Buch Andreasen, P., Hendel, J., Greisen, G., Hvidberg, E. F.: Pharmacokinetics of diazepam in disordered liver function. Europ. J. clin. Pharmacol. (in press 1976)

  • Dasberg, H. H., van der Kleijn, E., Guelen, P. J. R., van Praag, H. M.: Clin. Pharmacol. Ther. 15, 473–483 (1974)

    Google Scholar 

  • Garattini, S., Marcucci, F., Morselli, P. L., Mussini, E.: The significance of measuring blood levels of benzodiazepines. In: Biological effects of drugs in relation to their plasma concentrations, D. S. Davies and B. N. C. Prichard, eds., pp. 211–225. London: MacMillan 1973

    Google Scholar 

  • Ghoneim, M. M., Mewaldt, S. P., Ambre, J.: Plasma levels of diazepam and mood ratings. Anesth. Analg. 54, 173–177 (1975)

    Google Scholar 

  • Gibaldi, M., Perrier, D.: Pharmacokinetics, Vol. I. New York: Marcel Decker 1975

    Google Scholar 

  • Harder, F., Elsass, P., Hendel, J., Hvidberg, E. F., Hjørting Hansen, E.: Clinical and psychological effects of intravenous diazepam related to plasma levels. A controlled double blind, crossover study in oral surgery involving local analgesia. Int. J. oral Surg. (in press 1976)

  • Hendel, J.: Cumulation in cerebrospinal fluid of the N-desmethyl metabolite after long-term treatment with diazepam in man. Acta pharmacol. (Kbh.) 37, 17–32 (1975)

    Google Scholar 

  • hillestad, L., Hansen, T., Melsen, H., Drivener, A.: Diazepam metabolism in normal man. Clin. Pharmacol. Ther 16, 485–489 (1974)

    Google Scholar 

  • Van der Kleijn, E.: Pharmacokinetics of distribution and metabolism of ataractic drugs and an evaluation of the site of antianxiety activity. Ann. N. Y. Acad. Sci. 179, 115–125 (1971)

    Google Scholar 

  • Van der Kleijn E., Guelen, P. J. M., Beelen, T. C. M., Rijnties, N. V. M., Zuidgeest, T. L. B.: Kinetics of general and regional brain distribution of closely related 7-chloro-1,4-benzodiazepines. In: The benzodiazepines, S. Garattini, E. Mussini, and L. O. Randall, eds., pp. 145–164. New York: Raven Press 1973

    Google Scholar 

  • Klotz, U., Uvant, G. R., Hoyumpa, A., Achenker, S., Wilkinson, G. R.: The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J. clin. Invest. 55, 347–359 (1975)

    Google Scholar 

  • Laidlaw, J., Read, A. E., Sherlock, S.: Morphine tolerance in hepatic cirrhosis. Gastroenterology 40, 389–396 (1961)

    Google Scholar 

  • Morgan, M. H., Read, A. E.: Antidepressants and liver disease. Gut 13, 697–701 (1972)

    Google Scholar 

  • Morselli, P. L., Cassano, G. B., Placidi, G. F., Muscettola, G. B., Rizzo, M.: Kinetics of the distribution of 14C-Diazepam and its metabolites in various areas of cat brain. In: The benzodiazepines, S. Garattini, E. Mussini, and L. O. Randall, eds., pp. 129–143. New York: Raven Press 1973

    Google Scholar 

  • Read, A. E., Laidlaw, J., McCarthy, C. F.: Effects of chlorpromazine in patients with hepatic disease. Brit. med. J. 1969III, 497–499

  • De Renzi, E., Faglioni, P.: The comparative efficiency of intelligence and vigilance test in detecting hemispheric cerebral damage. Cortex 1, 410–433 (1965)

    Google Scholar 

  • Riegelmann, S., Loo, J. C. K., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci. 57, 717–756 (1968)

    Google Scholar 

  • Siegel, S.: Non parametric statistics. New York: McGraw Hill 1956

    Google Scholar 

  • Spielberger, C. D., Gorsuch, R. L., Lushene, R. E.: STAI manual for the state-trail anxiety inventory. Consulting Psychologists Press, Inc. Calif. 1970

    Google Scholar 

  • Tansella, M., Siciliani, O., Burti, L., Schiavon, M., Zimmermann Tansella, Ch., Gerna, M., Tognoni, G., Morselli, P. L.: N-desmethyl-diazepam and amylobarbitone sodium as hypnotics in anxious patients. Plasma levels clinical efficacy and residual effects. Psychopharmacologia (Berl.) 41, 81–85 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hendel, J., Elsass, P., Andreasen, P.B. et al. Neuropsychologic effects of diazepam related to single dose kinetics and liver function. Psychopharmacology 48, 11–17 (1976). https://doi.org/10.1007/BF00423300

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00423300

Key words

Navigation