Lorazepam
Lorazepam. Benzodiazepine with direct glucuronidation (no CYP metabolism, no active metabolites) — preferred in hepatic impairment + elderly.… Oral half-life 13 h.
Benzodiazepine with direct glucuronidation (no CYP metabolism, no active metabolites) — preferred in hepatic impairment + elderly. First-line for status epilepticus (faster CNS onset than diazepam and no long-acting metabolites).
PK: the whole record moves to Greenblatt 1982 (PMID:6121043), 10 healthy volunteers given 2 mg by five routes including intravenous — verbatim "elimination half-life (t 1/2 beta), 12.9 (+/- 0.8) hr", "volume of distribution, 1.3 (+/- 0.07) liters/kg" (91 L at 70 kg) and "Absolute systemic availability for trials B, C, D, and E averaged 95.9, 99.8, 94.1, and 98.2%". THE PREVIOUS IV CITATION GAVE NO INTRAVENOUS LORAZEPAM AT ALL — its only intravenous agent was ANTIPYRINE, a metabolic probe. The sublingual figure is narrowed to 0.941, an ordinary tablet held sublingually; 0.982 describes a specially formulated sublingual tablet. ka values dropped on both extravascular routes: 1.5 /h traces to a different drug 1.5-HOUR absorption half-life, and the paper own sublingual absorption half-life of 28.7 min gives 1.45 /h, not the stored 1.59.
Pharmacokinetics
- Oral — t½ 12.9 h · F 100%
- IV — t½ 12.9 h · F 100% · Vd 91 L
- Sublingual — t½ 12.9 h · F 94%
Sources: PMID:1684924, PMID:6121043, PMID:6131586