Benzodiazepine (and Barbiturate) Comparison

Author: Curtis Geier, PharmD
Updated: 1/15/2020


Clinical Implications [2, 10]

  • All benzodiazepines and barbiturates are metabolized by the liver.

    • Chlordiazepoxide, diazepam, midazolam, phenobarbital:

      Phase I metabolism (CYP450 system): Prolonged half-lives and durations of effect with hepatic dysfunction

    • Lorazepam:

      Phase II metabolism (glucuronidation): Less effect on pharmacokinetics with hepatic dysfunction.

Pharmacokinetics [1, 3-5, 10]

  • Benzodiazepines exert primary action in central nervous system
  • Drug permeability across the blood brain barrier influenced by the lipophilicity of molecule

    • A more lipophilic benzodiazepine will have a quicker onset once in systemic circulation.

      • IV speed of onset: Diazepam (fastest) > lorazepam (medium speed) > midazolam (slowest onset)
    • A more lipophilic benzodiazepine is more slowly absorbed following intramuscular administration, affecting the onset of action.

      • IM speed of onset: Midazolam (fastest) > lorazepam (medium speed)
      • Diazepam onset is variable because of unreliable IM absorption
    • A more lipophilic compound quickly diffuses out of the CNS and into lipid tissue, leading to short duration of action

      • Diazepam has a short duration of action with a single dose despite its long T1/2.
      • With repeated dosing the concentration will accumulate saturating the lipid tissue and protein binding, resulting in a longer effect duration approaching the T1/2.


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