Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients

Xenobiotica. 1987 Aug;17(8):1001-9. doi: 10.3109/00498258709044199.

Abstract

1. The pharmacokinetics of loprazolam and its principal pharmacologically active metabolite, the piperazine N-oxide, were compared in young subjects (aged 21-25 years) and elderly patients (aged 63-86 years) following single oral evening doses (0.5 mg and 1 mg). 2. Plasma loprazolam was assayed by a specific h.p.l.c./g.c. method. The N-oxide metabolite was assayed by gas chromography. 3. Mean times to peak plasma concentration of loprazolam did not differ significantly between young and elderly subjects and ranged from 1.6-2.7 h. There was, however, a longer mean time to peak concentration of the N-oxide metabolite in the elderly but this was only statistically different after the 0.5 mg dose (4.5 mg young, 6.4 h elderly). 4. Mean peak plasma concentrations of loprazolam did not differ significantly between young and elderly nor did plasma concentrations of the N-oxide metabolite. 5. Although the mean elimination half-life of loprazolam was not statistically significantly different between young and elderly subjects (range 10.9-16.0 h) there was a trend towards somewhat longer half-lives in the elderly. Furthermore, there was a small but significant increase in the half-life of the N-oxide metabolite in the elderly after the 1 mg dose from 11.7 h to 16.7 h. 6. The areas under the plasma concentration time curves for both loprazolam and its N-oxide were greater in the elderly being some 50-68% (mean 132.0 and 111.5 ng/ml h) above those found in young subjects (mean 89.8 and 66.0 ng/ml h).(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Adult
  • Aged
  • Aging / metabolism
  • Anti-Anxiety Agents / blood
  • Anti-Anxiety Agents / pharmacokinetics*
  • Benzodiazepines*
  • Benzodiazepinones / blood
  • Benzodiazepinones / pharmacokinetics*
  • Chromatography, Gas
  • Chromatography, High Pressure Liquid
  • Circadian Rhythm
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged

Substances

  • Anti-Anxiety Agents
  • Benzodiazepinones
  • Benzodiazepines
  • triazulenone