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Cotinine disposition and effects.

N L Benowitz, F Kuyt, P Jacob

    Clinical Pharmacology and Therapeutics
    |November 1, 1983
    PubMed
    Summary
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    Cotinine, nicotine's main metabolite, shows no cardiovascular effects in smokers. Its elimination is primarily metabolic, with renal clearance affected by urine pH.

    Area of Science:

    • Pharmacokinetics and Metabolism
    • Toxicology

    Background:

    • Cotinine is the primary metabolite of nicotine in humans.
    • Understanding cotinine's disposition is crucial for assessing smoking-related health effects.

    Purpose of the Study:

    • To investigate the pharmacokinetic disposition of cotinine in healthy smokers.
    • To evaluate the impact of urinary pH on cotinine's renal clearance.
    • To assess the cardiovascular and psychologic effects of cotinine at typical smoking exposure levels.

    Main Methods:

    • Intravenous infusion of cotinine fumarate in healthy habitual cigarette smokers.
    • Measurement of metabolic and renal clearance, volume of distribution, and terminal half-life.
    • Assessment of renal clearance under conditions of urinary acidification and alkalinization.

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  • Monitoring of cardiovascular parameters (heart rate, blood pressure, skin temperature) and subjective effects.

    • Main Results:

    • Mean metabolic clearance of cotinine was 60 ml/min, with renal clearance averaging 17% of total clearance.
    • Steady-state volume of distribution exceeded body weight.
    • Renal clearance significantly increased with urinary acidification but was unaffected by alkalinization.
    • Cotinine infusion did not elicit significant cardiovascular or psychologic effects.

    Conclusions:

    • Cotinine exhibits primarily metabolic clearance, with renal excretion influenced by urinary pH.
    • At typical exposure levels, cotinine demonstrates minimal cardiovascular and psychologic activity, unlike nicotine.