Obesity effects on nitrazepam disposition.

DR Abernethy, DJ Greenblatt, A. Locniskar, HR Ochs, JS Harmatz, RI Shader

Research output: Contribution to journalArticlepeer-review

Abstract

Nitrazepam pharmacokinetics were studied in 14 obese (mean +/‐ s.e. mean body weight 107 +/‐ 9 kg; percent ideal body weight [IBW] 166 +/‐ 12%) and 14 normal body weight (63 +/‐ 3 kg; percent IBW 98 +/‐ 2%) subjects. After an overnight fast, each subject ingested 10 mg nitrazepam orally. Nitrazepam concentrations were determined in plasma samples obtained over the following 72 h. Comparison of peak nitrazepam plasma concentration (94.2 +/‐ 10.3‐obese vs 119 +/‐ 14.6 ng ml‐1; NS) and time required after drug administration to reach peak concentration (1.52 +/‐ 0.24‐obese vs 1.59 +/‐ 0.36 h; NS) indicated no differences between obese and control subjects. Elimination half‐life was markedly increased in obese subjects (33.5 +/‐ 2.2 vs 23.9 +/‐ 1.2 h; P less than 0.001) due to increased apparent volume of distribution (Vd) (290 +/‐ 45 vs 137 +/‐ 12 l; P less than 0.005). Oral clearance was also increased in the obese subjects (101 +/‐ 12.4 vs 66.8 +/‐ 12.4 ml min‐ 1; P less than 0.02). Extent of nitrazepam binding to plasma proteins was slightly decreased in obese subjects (% unbound‐19.7 +/‐ 0.4‐obese vs 17.9 +/‐ 0.3%; P less than 0.005). Correction of both Vd (2.62 +/‐ 0.17‐obese vs 2.22 +/‐ 0.19 l kg‐1; NS) and clearance (0.93 +/‐ 0.06‐ obese +/‐ 1.07 +/‐ 0.07 ml min‐1 kg‐1; NS) for total body weight (TBW) suggested that increases in obese subjects of both of these parameters were a function of body weight.(ABSTRACT TRUNCATED AT 250 WORDS) 1986 The British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)551-557
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume22
Issue number5
DOIs
StatePublished - Nov 1986

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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