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Pethidine binding in plasma: effects of methodological variables.

C La Rosa, L E Mather, D J Morgan

    British Journal of Clinical Pharmacology
    |April 1, 1984
    PubMed
    Summary
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    Investigating plasma protein binding of [14C]-pethidine, this study found temperature and pH significantly influence results. Proper pH control is crucial, as previous lower estimates may be artifacts.

    Area of Science:

    • Pharmacology
    • Biochemistry
    • Analytical Chemistry

    Background:

    • Plasma protein binding is a critical determinant of drug disposition and efficacy.
    • Pethidine (meperidine) is an opioid analgesic with variable plasma protein binding reported in literature.
    • Methodological inconsistencies may contribute to discrepancies in reported pethidine binding values.

    Purpose of the Study:

    • To investigate methodological variables affecting in vitro [14C]-pethidine plasma protein binding.
    • To establish optimal conditions for accurate pethidine binding assays.
    • To identify potential sources of error in previous studies.

    Main Methods:

    • Equilibrium dialysis was employed to assess [14C]-pethidine binding.
    • Rigorous control of pH, temperature, ionic strength, and pethidine concentration was maintained.

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  • Plasma samples were analyzed under varying experimental conditions.

    • Main Results:

    • Ionic strength, pethidine concentration, and sample storage duration did not significantly impact binding.
    • Unbound pethidine fraction decreased with increasing temperature (25°C to 37°C).
    • Unbound fraction decreased with increasing pH (7.0 to 8.0), with a mean of 0.58 at pH 7.4 and 37°C.

    Conclusions:

    • Accurate pH control is essential for reliable pethidine plasma protein binding measurements.
    • Previous reports of lower pethidine unbound fractions (0.2-0.4) likely resulted from inadequate pH control.
    • Optimal in vitro conditions involve a pH of 7.4 and a temperature of 37°C for pethidine binding studies.