Diazepam kinetics in patients with renal insufficiency or hyperthyroidism.

HR Ochs, DJ Greenblatt, HJ Kaschell, U. Klehr, M. Divoll, DR Abernethy

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34 Scopus citations


1 Eight patients with end‐stage renal insufficiency on maintenance haemodialysis, and seven patients with newly diagnosed hyperthyroidism, received a single intravenous dose of diazepam, followed by blood sampling over the next 7 days. Fifteen healthy volunteer controls, matched with patients for age and sex, were similarly studied. 2 Diazepam half‐life in renal failure patients (mean 37 h) was greatly reduced compared to controls (mean 92 h, P less than 0.05) and clearance of total (free plus bound) diazepam correspondingly increased (0.94 v 0.34 ml min‐1 kg‐1, P less than 0.01). 3 However, differences were largely related to disease‐related changes in drug binding and distribution. Mean unbound fraction of diazepam in plasma of renal patients (7.0%) was greatly increased over controls (1.4%, P less than 0.01) and Vd of unbound diazepam greatly reduced (57 v 157 l/kg, P less than 0.01). 4 Clearance of pharmacologically active unbound diazepam (intrinsic clearance) was not significantly different between renal patients and controls (23 vs 30 ml min‐1 kg‐1). 5 None of the kinetic variables for total or unbound diazepam in thyrotoxic patients differed significantly from those in controls matched for age and sex. 6 End‐ stage renal failure (or its associated drug therapy) alters diazepam protein binding and distribution, but does not significantly change clearance of unbound drug. Thyrotoxicosis does not influence diazepam kinetics. 1981 The British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)829-832
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Issue number6
StatePublished - Dec 1981
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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