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Clonazepam serum protein binding during development.

G M Pacifici, G Taddeucci-Brunelli, A Rane

    Clinical Pharmacology and Therapeutics
    |March 1, 1984
    PubMed
    Summary
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    Clonazepam exhibits lower protein binding in umbilical cord serum compared to adults. This difference in binding capacity and affinity normalizes within the first year of life in children.

    Area of Science:

    • Pharmacology
    • Clinical Chemistry

    Background:

    • Understanding drug pharmacokinetics is crucial for safe and effective therapeutic use, especially in pediatric populations.
    • Clonazepam, a benzodiazepine, is widely prescribed, necessitating a clear understanding of its protein binding characteristics across different age groups.

    Purpose of the Study:

    • To investigate the differences in clonazepam protein binding in umbilical cord serum, children, and adults.
    • To characterize the kinetics of clonazepam serum protein binding, including binding capacity and affinity, in neonates and adults.

    Main Methods:

    • Protein binding of clonazepam was assessed in serum samples from umbilical cords, children (2 months to 12 years), and adults (27 to 40 years).
    • Kinetic parameters, including the number of binding sites (n) and association constant (K), were determined using double reciprocal plots.

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    Main Results:

    • The unbound fraction of clonazepam was significantly higher in umbilical cord serum (17.3%) than in adult serum (13.9%).
    • In children, unbound clonazepam levels reached adult values within the first year of life.
    • Adult serum demonstrated lower binding capacity (n) but higher affinity (K) for clonazepam compared to umbilical cord serum.

    Conclusions:

    • Neonatal serum exhibits reduced binding capacity and affinity for clonazepam compared to adult serum.
    • The pharmacokinetic profile of clonazepam in children matures rapidly, reaching adult levels of protein binding within the first year of life.