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Diazepam disposition determinants

D J Greenblatt, M D Allen, J S Harmatz

    Clinical Pharmacology and Therapeutics
    |March 1, 1980
    PubMed
    Summary
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    Diazepam pharmacokinetics differ by age and sex. Elderly individuals and females exhibit larger volume of distribution and altered clearance, impacting drug dosing. Smoking also influences diazepam clearance.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacology
    • Drug Metabolism

    Background:

    • Diazepam pharmacokinetics can vary significantly based on demographic factors.
    • Understanding these variations is crucial for optimizing therapeutic drug use.

    Purpose of the Study:

    • To investigate the influence of age and sex on diazepam kinetics in healthy adults.
    • To determine how factors like plasma protein binding and smoking affect diazepam disposition.

    Main Methods:

    • A single intravenous dose of diazepam was administered to four groups of healthy subjects: young males, young females, elderly males, and elderly females.
    • Plasma diazepam concentrations were measured over 9 days using electron-capture gas-liquid chromatography.
    • Volume of distribution (Vd) and clearance were calculated, considering both total and unbound drug concentrations.

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    Main Results:

    • Volume of distribution (Vd) for total diazepam increased with age and in females.
    • Clearance of total diazepam was similar in young and elderly females but higher in young males compared to elderly males.
    • The unbound fraction of diazepam was higher in the elderly, linked to lower albumin levels.
    • Intrinsic clearance of unbound diazepam was higher in females than males and in younger than older individuals.
    • Smoking was associated with increased clearance, especially in younger subjects.

    Conclusions:

    • Age and sex significantly impact diazepam's volume of distribution and clearance.
    • Elderly individuals and females may require dose adjustments due to altered diazepam pharmacokinetics.
    • Plasma protein binding, particularly albumin levels, plays a role in diazepam disposition, especially in the elderly.