LiverInOut copyWe sometimes hear information stated as fact that may not be entirely accurate. One such example is, “I’m going to use lorazepam because it isn’t metabolized by the liver.”

Let’s set the record straight.

ALL benzodiazepines are metabolized by the liver. 

Benzodiazepines and 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

These do not have active metabolites, and the half-life remains relatively the same even in the setting of liver disease.

The rest of the benzodiazepines are primarily metabolized via hepatic CYP-mediated oxidation. These may have prolonged duration of effect in patients with marked liver impairment, particularly the drugs with active metabolites such as diazepam, clonazepam, and midazolam. Some practitioners like to take advantage of the longer duration of action and active metabolites. Others prefer to have more predictable kinetics in patients with liver disease and stick with the ‘LOT’ options.

Bottom Line

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

Further Reading

  1. 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. http://www.accesspharmacy.com/content.aspx?aID=16663643. Accessed November 7, 2013.
  2. 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. http://www.accesspharmacy.com/content.aspx?aID=6520459. Accessed November 7, 2013.

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Bryan D. Hayes, PharmD, FAACT, FASHP

Bryan D. Hayes, PharmD, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules series, ALiEMU
Attending Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
Bryan D. Hayes, PharmD, FAACT, FASHP

@PharmERToxGuy

EM Pharmacist & Toxicologist @MassGeneralEM | Asst Prof @HarvardMed/@EMRES_MGHBWH | @ALiEMteam leadership | Capsules creator, ALiEMU | President, ABAT | #FOAMed