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Plasma total phenytoin: a possibly misleading test in developing countries
1Department of Chemical Pathology, SAIMR and the University of the Witwatersrand Medical School, Gauteng, South Africa.
Insights
In South Africa, many rural black patients have low albumin levels, affecting phenytoin drug levels. Corrected phenytoin values, not total, should be reported in hypoalbuminemic populations for accurate dosing.
Area of Science:
- Pharmacology
- Clinical Chemistry
- Public Health
Background:
- Phenytoin use is rising in rural South African populations.
- Hypoalbuminemia is prevalent due to malnutrition and disease, impacting drug efficacy.
- Low albumin concentrations affect the free fraction of phenytoin in the extracellular fluid.
Purpose of the Study:
- To assess the extent of hypoalbuminemia in this population.
- To compare measured total phenytoin with corrected phenytoin values.
- To determine the clinical relevance of reporting corrected phenytoin levels.
Main Methods:
- Patient albumin concentrations were measured.
- Total phenytoin levels were determined by immunoassay.
- Corrected phenytoin levels were calculated using the Sheiner-Tozer equation.
Main Results:
- A significant proportion of patients exhibited hypoalbuminemia.
- Differences between total and corrected phenytoin values exceeded 20% in 37% of patients.
- This highlights potential inaccuracies in total phenytoin reporting.
Conclusions:
- Hypoalbuminemia significantly impacts phenytoin levels in this population.
- Corrected phenytoin values are more clinically relevant than total values.
- Reporting corrected phenytoin is recommended for hypoalbuminemic patient populations.
Abstract:
The use of phenytoin has increased among the rural black population in South Africa, many of whom have albumin concentrations below the accepted reference range of 35-50 g/L, related to a combination of malnutrition and late-presenting renal and hepatic disease. Because albumin concentration has a major effect on the proportion of free phenytoin in the extracellular fluid, we instituted a study of the extent of hypoalbuminemia and of the difference between "total" phenytoin (measured by immunoassay), and "corrected" phenytoin (calculated using the Sheiner-Tozer equation, which is based on a mean albumin of 40 g/L). The differences were significant (higher than 20%) in 37% of patients and led us to propose that in populations in which there is a high proportion of patients who are hypoalbuminemic, it is corrected rather than total phenytoin that should be the value reported.