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Related Experiment Videos

Cimetidine clearance in the obese.

L A Bauer, C Wareing-Tran, W A Edwards

    Clinical Pharmacology and Therapeutics
    |April 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

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    Obese individuals exhibit altered cimetidine pharmacokinetics, with higher systemic and renal clearances. Dosage adjustments may be needed for obese patients to achieve therapeutic cimetidine levels.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacology
    • Drug Metabolism

    Background:

    • Obesity can significantly alter drug pharmacokinetics, affecting drug distribution, metabolism, and excretion.
    • Understanding pharmacokinetic changes in obese individuals is crucial for optimizing drug dosing and ensuring therapeutic efficacy.
    • Cimetidine, a widely used H2 receptor antagonist, has a pharmacokinetic profile that may be influenced by body weight.

    Purpose of the Study:

    • To investigate the pharmacokinetic differences of cimetidine in normal weight versus obese subjects.
    • To determine if cimetidine clearance and volume of distribution are altered by obesity.
    • To assess the implications of these pharmacokinetic changes for cimetidine dosing in obese populations.

    Main Methods:

    • A single intravenous infusion of 600 mg cimetidine was administered to six normal weight and six obese subjects.

    Related Experiment Videos

  • Subjects were matched for age, sex, height, and renal function (normal serum creatinine levels).
  • Pharmacokinetic parameters including systemic clearance, renal clearance, volume of distribution, and half-life were determined.

    • Main Results:

    • Obese subjects demonstrated significantly higher cimetidine systemic clearance (1147 vs. 637 ml/min) and renal clearance (808 vs. 318 ml/min) compared to normal weight subjects.
    • The volume of distribution at steady state was similar between groups (82 vs. 84 L), but the half-life was shorter in obese subjects (1.2 vs. 1.9 hr).
    • Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 vs. 509 ml/min).

    Conclusions:

    • Obesity leads to increased cimetidine systemic and renal clearance, likely due to enhanced renal excretion.
    • Standard cimetidine dosing may result in sub-therapeutic concentrations in obese individuals due to these altered pharmacokinetic parameters.
    • Weight-normalized dosing, particularly using exponents like 0.76, may be necessary to achieve comparable cimetidine serum concentrations in both normal weight and obese patients.