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Related Experiment Videos

Etretinate kinetics during chronic dosing in severe psoriasis.

J Massarella, F Vane, C Buggé

    Clinical Pharmacology and Therapeutics
    |April 1, 1985
    PubMed
    Summary

    Etretinate pharmacokinetics in psoriasis patients show a significant increase in half-life (t1/2) from 7 hours after a single dose to 120 days after chronic dosing due to drug accumulation, not altered kinetics.

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    Area of Science:

    • Pharmacology
    • Dermatology
    • Clinical Chemistry

    Background:

    • Psoriasis is a chronic inflammatory skin condition.
    • Etretinate is a retinoid used in psoriasis treatment.
    • Understanding drug pharmacokinetics is crucial for effective therapy.

    Purpose of the Study:

    • To characterize the pharmacokinetics of etretinate in psoriasis patients.
    • To evaluate etretinate's absorption, distribution, metabolism, and excretion (ADME) over 6 months of therapy.
    • To determine the drug's elimination half-life before, during, and after treatment.

    Main Methods:

    • Fourteen psoriasis patients received a single 100 mg dose, followed by 6 months of multiple dosing (25 mg, 1-4 times daily).
    • Blood samples were collected at various intervals for up to 8 months post-treatment.

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  • Etretinate blood concentrations were quantified using a reverse-phase gradient elution HPLC assay.

    • Main Results:

    • The apparent elimination half-life (t1/2) of etretinate increased significantly from approximately 7 hours after a single dose to about 120 days after the last dose.
    • This lengthening of t1/2 is attributed to drug accumulation in blood, not changes in drug kinetics.
    • Etretinate blood concentration-time data fit a single polyexponential kinetic equation, indicating linear kinetics during the observed dosing regimens.

    Conclusions:

    • Etretinate exhibits linear kinetics during chronic dosing in psoriasis patients.
    • Drug accumulation significantly prolongs the apparent elimination half-life, impacting dosing and washout periods.
    • Single-dose pharmacokinetic data may not accurately predict steady-state concentrations during long-term etretinate therapy.