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Variability of Phenytoin Protein Binding in Epilepsy

W. Garth Rapeport, MB, BCh, MRCP
Arch Neurol. 1984;41(4):363-363. doi:10.1001/archneur.1984.04050160025007
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To the Editor.  —A number of problems arise from the study of DeMonaco and Lawless.1 Blood samples for measurement of free phenytoin levels were drawn into heparinized tubes. This practice may introduce a major flaw in the estimation of free drug levels,2,3 accounting for the discrepancy between predicted and measured free phenytoin concentrations. Lunde et al4 showed the importance of measuring free phenytoin concentrations at 37 °C; however, they did not indicate the temperature at which ultrafiltration was performed. DeMonaco and Lawless did not mention whether samples were taken from patients in the fasting state, as endogenous free fatty acids may displace phenytoin from binding sites.3 The authors also failed to provide precise data for the measurement of free phenytoin levels with the enzyme-multiplied immunoassay technique (EMIT) using the modified dilution procedure.The authors concluded that free phenytoin concentrations provide a more appropriate guide to monitoring

REFERENCES

DeMonaco HJ, Lawless LM:  Variability of phenytoin protein binding in epileptic patients . Arch Neurol 1983;;40:481-483.
Giacomini K, Giacomini J, Blashke T:  Heparin decreases plasma protein binding of drugs . Clin Pharmacol Ther 1980;;27:265.
Perucca E:  Plasma protein binding of phenytoin in health and disease: Relevance to therapeutic drug monitoring . Ther Drug Monit 1980;; 2:331-334.
Lunde PKM, Rane E, Yaffe ST, et al:  Plasma protein binding of diphenylhydantoin in man: Interaction with other drugs and the effect of temperature and plasma dilution . Clin Pharmacol Ther 1970;;11:846-855.

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DeMonaco HJ, Lawless LM:  Variability of phenytoin protein binding in epileptic patients . Arch Neurol 1983;;40:481-483.
Giacomini K, Giacomini J, Blashke T:  Heparin decreases plasma protein binding of drugs . Clin Pharmacol Ther 1980;;27:265.
Perucca E:  Plasma protein binding of phenytoin in health and disease: Relevance to therapeutic drug monitoring . Ther Drug Monit 1980;; 2:331-334.
Lunde PKM, Rane E, Yaffe ST, et al:  Plasma protein binding of diphenylhydantoin in man: Interaction with other drugs and the effect of temperature and plasma dilution . Clin Pharmacol Ther 1970;;11:846-855.

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