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Clinical Pharmacokinetics of Diazepam

Clinical Pharmacokinetics volume 3, pages 72–91 (1978)Cite this article

Summary

Diazepam is still one of the most used of the benzodiazepine group of drugs. Extensive studies over 10 years have defined a fairly complete profile of its kinetics. Minor aspects relating to patterns of its metabolism and excretion in certain age groups and in some disease states remain to be described quantitatively. However, there is more than sufficient kinetic information available for the requirements of good clinical practice.

For optimum clinical benefit with minimum side-effects the following kinetic properties should be borne in mind: (a) there is a large interindividual variation (up to 30-fold) in dose/blood level ratios, especially when treatment is short-term; (b) the elimination half-life is prolonged in the elderly and the newborn and in some cases of liver disease; (c) there is accumulation of the active N-desmethylated metabolite during long-term treatment; and (d) administration of diazepam to pregnant women leads to rapid distribution from the maternal to fetal compartment: accumulation of both diazepam and desmethyldiazepam could cause prolonged sedation in the newborn. As there does not appear to be any clear relationship between the concentration of diazepam in the plasma and clinical effect, measurement of blood levels, other than for research purposes, is unnecessary.

Based on kinetic data, a single administration of diazepam at night should be adequate for hypnotic and anxiolytic effects in most patients.

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  1. Istituto di Ricerche Farmacologiche ‘Mario Negri’, 20157, Milan, Via Eritrea, 62, Italy

    Marinella Mandelli, Gianni Tognoni & Silvio Garattini

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  1. Marinella Mandelli
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  2. Gianni Tognoni
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Mandelli, M., Tognoni, G. & Garattini, S. Clinical Pharmacokinetics of Diazepam. Clin Pharmacokinet 3, 72–91 (1978). https://doi.org/10.2165/00003088-197803010-00005

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Keywords

  • Diazepam
  • Clinical Pharmacology
  • Clinical Pharmacokinetic
  • Oxazepam
  • Enterohepatic Circulation