Effect of age, gender, and obesity on midazolam kinetics

D. J. Greenblatt, D. R. Abernethy, A. Locniskar, J. S. Harmatz, R. A. Limjuco, R. I. Shader

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428 Scopus citations


The effects of age, sex, and obesity on the kinetics of single intravenous (iv) and oral doses of midazolam were evaluated in healthy volunteers who received 2.5-5 mg of iv midazolam on one occasion and 5-10 mg orally on another. Kinetics were determined from multiple plasma midazolam concentrations measured during 24 h after dosage. Midazolam elimination half-life (t(1/2)) after iv dosage was significantly prolonged in elderly (aged 60-74 yr) versus young (24-33 yr) males (5.6 vs. 2.1 hours, P <0.01) and total clearance was significantly reduced (4.4 vs. 7.8 ml·min-1·kg-1, P <0.01), leading to increased systemic availability of the oral dose (50% vs. 41%, P <0.05). However total volume of distribution calculated by the area method (V(d)) (1.6 vs. 1.3 l/kg) and protein binding (3.5 vs. 3.4% unbound) did not differ between groups. Among women there were no significant differences between elderly (64-79 yr) and young (23-37 yr) volunteers in t(1/2) (4.0 vs. 2.6 h), clearance (7.5 vs. 9.4 ml·min-1·kg-1), V(d) (2.1 vs. 2.0 l/kg), protein binding (3.7% vs. 3.7% unbound), or oral bioavailability (38% vs. 36%). In obese volunteers (mean weight 117 kg; 173% of ideal weight) versus control subjects of normal weight (66 kg, 95% of ideal weight) matched for age, sex, and smoking habits, midazolam V(d) was increased significantly (311 vs. 114 l, P <0.001). V(d) was greater in the obese subjects even after correction for total weight (2.7 vs. 1.7 l/kg, P <0.001), indicating disproportionate distribution of midazolam into adipose weight. Since clearance was not different between groups (472 vs. 530 ml/min), the prolonged t(1/2) in obese subjects (8.4 vs. 2.7, P <0.001) was due to the increased V(d). The clinical consequences of age- and obesity-related changes in midazolam kinetics will depend on the circumstances of administration.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
Issue number1
StatePublished - 1984

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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