Abstract
The primary pharmacologic actions of the benzodiazepine derivatives include: reduction of anxiety, induction of sleep, and anti-seizure effects. Establishing kinetic-dynamic relationships for this class of drugs is a particular challenge, since reliable quantitation of these primary pharmacologic actions is difficult to achieve. This chapter reviews methodologic issues in studying the pharmacokinetic profile and the pharmacodynamic properties of benzodiazepine derivatives, and methods for quantitative linkage of plasma concentrations with clinical effects.
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References
Ballenger, J. C., G. D. Burrows, R. L. DuPont, I. M. Lesser, R. Noyes, Jr., J. C. Pecknold, A. Rifkin, and R. P. Swinson (1988). Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment. Arch. Gen. Psychiatry, 45, 413–422.
Barnhill, J. G., D. J. Greenblatt, L. G. Miller, A. Gaver, J. S. Harmatz and R. I. Shader (1990). Kinetic and dynamic components of increased benzodiazepine sensitivity in aging animals. J. Pharmacol. Exp. Ther., 253 1153–1161.
Ghoneim, M. M., and S. P. Mewaldt (1990). Benzodiazepines and human memory: a review. Anesthesiology, 72 926–938.
Greenblatt, D. J., and V. H. Sethy (1990). Benzodiazepine concentrations in brain directly reflect receptor occupancy: studies of diazepam, lorazepam, and oxazepam. Psycho-pharmacology, 102 373–378.
Greenblatt, D. J., and R. I. Shader (1987). Pharmacokinetics of antianxiety agents. In H. Y. Meltzer (Ed.), Psychopharmacology: The Third Generation of Progress. Raven Press, New York. pp. 1377–1386.
Greenblatt, D. J., R. I. Shader, and D. R. Abernethy (1983). Current status of benzodiazepines. N. Engl. J. Med., 309 354–358, 410–416.
Greenblatt, D. J., B. L. Ehrenberg, J. Gunderman, A. Locniskar, J. M. Scavone, J. S. Harmatz, and R. I. Shader (1989a). Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clin. Pharmacol. Ther., 45 356–365.
Greenblatt, D. J., B. L. Ehrenberg, J. Gunderman, J. M. Scavone, N. T. Tai, J. S. Harmatz, and R. I. Shader (1989b). Kinetic and dynamic study of intravenous lorazepam: comparison with intravenous diazepam. J. Pharmacol. Exp. Ther., 250 134–140.
Greenblatt, D. J., J. S. Harmatz, and R. I. Shader (1991a). Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Parts I and II). Clin. Pharmacokinet. 21, 165–177, 262–273.
Greenblatt, D.J., J. S. Harmatz, L. Shapiro, N. Engelhardt, T. A. Gouthro and R. I. Shader (1991b). Sensitivity to triazolam in the elderly. N. Engl. J. Med. 324, 1691–1698.
Hommer, D. W., V. Matsuo, O. Wolkowitz, G. Chrousos, D. J. Greenblatt, H. Weingartner, and S. M. Paul (1986). Benzodiazepine sensitivity in normal human subjects. Arch. Gen. Psych.. 43 542–551.
Johnson, L. C., and D. A. Chernik (1982). Sedative-hypnotics and human performance. Psychopharmacology, 76 101–113.
Koelega, H. S. (1989). Benzodiazepines and vigilance performance: a review. Psychopharmacology, 98 145–156.
Lapierre, K. A., D. J. Greenblatt, J. E. Goddard, J. S. Harmatz, and R. I. Shader (1990). The neuropsychiatric effects of asparatame in normal volunteers. J. Clin. Pharmacol. 30, 454–460.
Miller, L. G., D. J. Greenblatt, J. G. Barnhill, and R. I. Shader (1988). Chronic benzodiazepine administration. I. Tolerance is associated with benzodiazepine receptor downregulation and decreased gamma-aminobutyric acidA receptor function. J. Pharmacol. Exp. Ther., 246 170–176.
Miller, L. G., D. J. Greenblatt, S. M. Paul, and R. I. Shader (1987). Benzodiazepine receptor occupancy in vivo: correlation with brain concentrations and pharmacodynamic actions. J. Pharmacol. Exp. Ther., 240 516–522.
Roy-Byrne, P. P., D. S. Cowley, D. J. Greenblatt, and R. I. Shader (1990). Reduced benzodiazepine sensitivity in panic disorder. Arch. Gen. Psychiatry. 47 534–540.
Smith, R. B., and P. D. Kroboth (1987). Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology 93,105–112.
Smith, R. B., P. D. Kroboth, J. T. Vanderlugt, J. P. Phillips, and R. P. Juhl (1984). Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology, 48 452–456.
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© 1993 Springer Science+Business Media New York
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Greenblatt, D.J. (1993). The Benzodiazepines: Kinetic-Dynamic Relationships. In: Yacobi, A., Skelly, J.P., Shah, V.P., Benet, L.Z. (eds) Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1520-0_23
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DOI: https://doi.org/10.1007/978-1-4757-1520-0_23
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