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Obesity effects on nitrazepam disposition.

D R Abernethy, D J Greenblatt, A Locniskar

    British Journal of Clinical Pharmacology
    |November 1, 1986
    PubMed
    Summary
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    Obese individuals exhibit a significantly longer nitrazepam elimination half-life due to increased volume of distribution, impacting drug clearance. These pharmacokinetic changes in obese subjects are related to total body weight.

    Area of Science:

    • Pharmacokinetics
    • Obesity research
    • Clinical pharmacology

    Background:

    • Nitrazepam is a commonly prescribed benzodiazepine.
    • Obesity can alter drug pharmacokinetics, affecting efficacy and safety.
    • Understanding nitrazepam's behavior in obese individuals is crucial for appropriate dosing.

    Purpose of the Study:

    • To investigate and compare the pharmacokinetics of nitrazepam in obese versus normal-weight individuals.
    • To determine how body weight influences nitrazepam's absorption, distribution, metabolism, and excretion.

    Main Methods:

    • 14 obese and 14 normal-weight subjects received a 10 mg oral dose of nitrazepam.
    • Plasma nitrazepam concentrations were measured over 72 hours.
    • Key pharmacokinetic parameters including half-life, volume of distribution, and clearance were calculated.

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    Main Results:

    • No significant differences were observed in peak plasma concentration or time to peak concentration between groups.
    • Obese subjects showed a markedly increased elimination half-life (33.5 vs 23.9 h) and volume of distribution (290 vs 137 L).
    • Oral clearance was increased in obese subjects, and plasma protein binding was slightly decreased.

    Conclusions:

    • Nitrazepam's elimination half-life is significantly prolonged in obese individuals.
    • Increased volume of distribution is the primary factor contributing to the prolonged half-life in obesity.
    • Pharmacokinetic changes in obese subjects appear to be a function of total body weight.