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Serum protein binding of phenytoin, diazepam and propranolol in age-related decrease in renal function
Annals of Clinical Research
|January 1, 1987
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.
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.
- 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.