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Mathematical model for cyclocytidine pharmacokinetics

K J Himmelstein, J F Gross

    Journal of Pharmaceutical Sciences
    |October 1, 1977
    PubMed
    Summary
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    Cyclocytidine acts as a reservoir for cytarabine in the body, releasing it over time. This pharmacokinetic model reveals cyclocytidine’s role in sustained cytarabine delivery, particularly at lower plasma concentrations.

    Area of Science:

    • Pharmacokinetics
    • Physiological modeling
    • Drug metabolism

    Background:

    • Cyclocytidine is a prodrug with potential therapeutic applications.
    • Understanding its in vivo behavior is crucial for optimizing drug delivery.
    • Cytarabine, a metabolite, is key to cyclocytidine's activity.

    Purpose of the Study:

    • To model the pharmacokinetics of cyclocytidine in humans.
    • To investigate the relationship between cyclocytidine and cytarabine concentrations.
    • To elucidate the role of cyclocytidine as a drug reservoir.

    Main Methods:

    • Physiological and anatomical modeling approach.
    • Compartmental modeling representing tissues and circulatory system.
    • Numerical solution of ordinary differential equations for drug concentration prediction.

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    Main Results:

    • Cyclocytidine and cytarabine models linked by a hydrolysis term.
    • Model predicts drug concentrations in situ using physiological parameters.
    • Cyclocytidine demonstrated potential as an in vivo reservoir for cytarabine.

    Conclusions:

    • Cyclocytidine can serve as a sustained-release reservoir for cytarabine.
    • This reservoir effect is significant at longer times and lower plasma concentrations.
    • The pharmacokinetic model provides insights into cyclocytidine-cytarabine dynamics.