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Serum protein binding of phenytoin, diazepam and propranolol in age-related decrease in renal function.

E Tiula1, S Elfving

  • 1Department of Clinical Pharmacology, University of Helsinki, Finland.

Annals of Clinical Research
|January 1, 1987
PubMed
Summary

In elderly individuals, reduced kidney function and low albumin levels increase unbound phenytoin and diazepam. Propranolol binding is primarily affected by alpha-1-acid glycoprotein levels.

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Area of Science:

  • Pharmacology
  • Geriatrics
  • Clinical Chemistry

Background:

  • Aging is associated with physiological changes, including decreased renal function and altered serum protein levels.
  • These changes can significantly impact the pharmacokinetics and pharmacodynamics of highly protein-bound drugs.
  • Understanding drug-protein binding in the elderly is crucial for optimizing therapeutic outcomes and minimizing adverse effects.

Purpose of the Study:

  • To investigate the in vitro serum protein binding of phenytoin, diazepam, and propranolol in elderly individuals with age-related renal impairment.
  • To identify the specific serum proteins and renal function markers that influence the free fraction of these drugs in the elderly population.

Main Methods:

  • A pressure ultrafiltration method was employed at 37°C to determine the unbound fraction of phenytoin, diazepam, and propranolol.

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  • Serum samples were collected from 32 elderly patients (mean age 88 years) with reduced renal function (mean 51Cr-EDTA clearance 46 ml/min).
  • Serum albumin, alpha-1-acid glycoprotein, urea, and creatinine concentrations were measured and correlated with drug free fractions.

    • Main Results:

    • Phenytoin free fraction correlated negatively with serum albumin and positively with serum urea levels.
    • Diazepam free fraction was significantly influenced by serum urea levels, even after correcting for albumin.
    • Propranolol free fraction showed a significant correlation only with alpha-1-acid glycoprotein concentration.

    Conclusions:

    • Age-dependent decreases in renal function, along with hypoalbuminemia, contribute to increased free fractions of phenytoin and diazepam in the elderly.
    • Serum urea concentration is a key determinant of phenytoin and diazepam free fractions in this population.
    • Alpha-1-acid glycoprotein concentration is the primary factor influencing propranolol free fraction in elderly individuals with renal impairment.