Age difference in kinetics of diazepam and lorazepam in man.

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概要

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• The effect of age on the pharmacokinetics of two benzodiazepines, diazepam andlorazepam, was studied.<BR>Seven young healthy male volunteers, 22 to 25 years old, and 10 elderly people, aged67 to 90, participated in this study after giving informed written consent. One mg oflorazepam was administered orally to the elderly volunteers, and 2 mg was given to theyoung volunteers. Using two weeks drug-free interval, 5 mg of diazepam was administeredorally to the two groups using randomized experimental protocol based on a Latin squaredesign.<BR>Blood samples were drawn for 72 hr and plasma concentrations of diazepam, N-desmethyldiazepam, and lorazepam were determined by electron-capture gas-liquid chromatography. Pharmacokinetic parameters were calculated and comparisons were madebetween the young and the elderly.<BR>With diazepam, elimination half. lives (t<SUB>1/2</SUB>) of the elderly group (Mean±SD: 86 .3±65.4 hr) were prolonged compared with those of the young (38.6±8.2 hr) at the 5%significance level.<BR>The volumes of distribution (V<SUB>d</SUB>) of diazepam in the elderly (1.42±0.83<I>l</I>/kg) weresignificantly larger than those of the young (0.79±0.20) (P<0.05). The t<SUB>1/2</SUB> and V<SUB>d</SUB> oflorazepam in the elderly (29.6±16.7 hr, 1.35±0.46<I>l</I>/kg respectively), were not significantlydifferent from those of the young (18.4±3.7 hr, 1.48±0.58<I>l</I>/kg respectively); however, clearance of lorazepam in the young (57.03±21.09ml/hr/kg) was higher than in theelderly (35.42±10.63ml/hr/kg) (P<0.05). Clearances of diazepam in the young and inthe elderly were nearly identical.

• 一般社団法人 日本臨床薬理学会の論文

著者

• Nakano Shigeyuki

  Department Of Clinical Pharmacology And Therapeutics Oita Medical University

• Honda Yumiko

  Department Of Physics Faculty Of Science Ochanomizu University

• Fukuda Tamotsu

  Department Of Pharmacy Ehime University School Of Medicine

• TOYOSHIMA Atsushi

  Department of Chemistry, Graduate School of Science, Osaka University

• MINESHITA Satoru

  Department of Clinical Pharmacology, Medical Research Institute, Tokyo Medical and Dental University

• NAKANO Shigeyuki

  Department of Pharmacology Ehime University, School of Medicine

• YANAIBARA Hiroshi

  Department of Hospital Pharmacy, Ehime University Hospital

• TAKANO Kikuo

  Department of Medicine, School of Medicine, Juntendo University

• TAKANO Kikuo

  Department of Geriatrics, Sohsen Hospital

• FUKUDA Tamotsu

  Department of Hospital Pharmacy, Okayama University Medical School

• FUKUDA Tamotsu

  Department of Hospital Pharmacy, Ehime University Hospital

• HONDA Yumiko

  Department of Medicine, Aoyama Kyosai Hospital

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