Table 1.
Pharmacodynamic and pharmacokinetic parameters of benzodiazepines
| Medication | Equivalent potency (mg) | Metabolism | Elimination half-life (hours) | Onset after oral dose consumption (hours) | Commentsa |
|---|---|---|---|---|---|
| Chlordiazepoxide | 50 | Oxidation by CYP3A4 to active metabolites (desmethyldiazepam) | 30–100 | 1 | Special attention should be paid to elderly patients, those with liver disease, persons taking other drugs interfering with BZD metabolism, or those who are poor metabolizers |
| Oxazepam | 30 | Non-CYP glucuronidation in liver to non-active metabolites | 5–15 | 1–2 | Preferred in patients with liver disease and in the elderly |
| Flurazepam | 30 | Oxidation by CYP3A4 to active metabolites (desalkylflurazepam, hydroxyethylflurazepam) | 40–114 (120–160 in older adults) | 0.5–1 | – |
| Temazepam | 30 | Primarily non-CYP glucuronidation in liver to minimally active metabolite | 8–20 | 0.5–1 | Preferred in patients with liver disease and in the elderly |
| Clorazepate | 15 | Oxidation by CYP3A4 to active metabolites (desmethyldiazepam) | 30–200 | 0.5–1 | – |
| Quazepam | 15 | Oxidation by CYP3A4 and non- CYP metabolism in liver to active metabolites (2-Oxoquazepam, Ndesalkyl-2-oxoquazepam) | 28–100 (190 in older adults) | 1 | – |
| Diazepam | 10 | Oxidation by CYP2C19 and CYP3A4 to active metabolites (desmethyldiazepam) | 50–100 (prolonged in older adults and renal or hepatic impairment) | 0.25–0.5 | Special attention should be paid to elderly patients, those with liver disease, persons taking other drugs interfering with benzodiazepine metabolism, or those who are poor metabolizers |
| Lorazepam | 1.5–2 | Non-CYP glucuronidation in liver to non-active metabolites | 10–20 | 0.5–1 | Preferred in patients with liver disease and in the elderly |
| Alprazolam | 1 | Oxidation by CYP3A4 to minimally active metabolites | 11–15 (16 in older adults, 20 in hepatic impairment, 22 in obesity) | 1 | – |
| Clonazepam | 0.5 | Oxidation and reduction by CYP3A4 | 18–50 | 0.5–1 | – |
| Estazolam | 0.3 | Oxidation by CYP3A4 to minimally active metabolites | 10–24 | 0.5–1 | – |
| Triazolam | 0.25 | Oxidation by CYP3A4 to minimally active metabolites | 1.5–5 | 0.25–0.5 | – |
| Midazolam | – | Oxidation by CYP3A4 to non- active metabolites | 1–4 | 0.1–0.3 | – |
Notes:
a
The drugs in this category have interactions with other CNS depressants such as alcohol and barbiturates and their concurrent use can lead to CNS and respiratory depression. Another significant drug interaction includes inhibitors (azole antifungals) or inducers of CYP3A4 especially in the case of diazepam and chlordiazepoxide.
Abbreviations: BZD, benzodiazepine; CNS, central nervous system.