Benzodiazepine Metabolism by the Liver

Take Home Points

• ALL benzodiazepines are metabolized by the liver. Some are just metabolized by different pathways that are less dependent on global liver function.

• The ‘LOT’ drugs are those metabolized mostly by conjugation.

  • L – Lorazepam
  • O – Oxazepam
  • T – Temazepam

• The ‘LOT’ drugs do not have active metabolites after hepatic conjugation, and therefore have minimally affected half-lives in patients with liver disease.

Non-LOT Benzodiazepine Medications

These benzodiazepines may have prolonged effects in patients with marked liver disease.

• Primarily metabolized via hepatic CYP-mediated oxidation.
• Examples: Drugs with active metabolites include -
  • Diazepam
  • Clonazepam
  • Midazolam

Some practitioners like to take advantage of the longer duration of action and active metabolites.

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References

• Mihic SJ, Harris RA. Chapter 17. Hypnotics and Sedatives. In: Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011. Accessed November 7, 2013.
• Lee DC, Ferguson KL. Chapter 74. Sedative-Hypnotics. In: Lee DC, Ferguson KL, eds.Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. Accessed November 7, 2013.