Plasma protein binding of phenytoin in the aged: in vivo studies.

Patterson, Marc C.; Heazelwood, R.; Smithurst, B. A.; Eadie, M. J.

doi:10.1111/j.1365-2125.1982.tb01396.x

Cited by 37 publications

(12 citation statements)

References 13 publications

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“…These changes involving highly protein-bound drug involve only a small number of blood samples within each resident and cannot account for all of the variability in these residents or for the variability in total PHT concentrations in most of the residents in our study. The elderly exhibit reduced PHT binding and an increased free fraction (unbound PHT concentration/ total PHT concentration), 15,16 as well as reduced serum albumin levels. 17 Increased PHT free fraction can result in unbound PHT concentrations that are higher than would be predicted from total serum concentrations and result in the patient exhibiting toxicity at total PHT concentrations that are within the adult therapeutic range.…”

Section: Abstract-backgroundmentioning

confidence: 99%

Variability of total phenytoin serum concentrations within elderly nursing home residents

Hardie

Leppik²,

Conway³

et al. 2003

Neurology

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Section: Abstract-backgroundmentioning

confidence: 99%

Variability of total phenytoin serum concentrations within elderly nursing home residents

Hardie

Leppik²,

Conway³

et al. 2003

Neurology

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“…11 A wide age range (0-18 years) was arbitrarily chosen in our study. And although differences in albumin concentrations may be the dominant factor explaining age differences in protein binding of phenytoin, the wide age range may be a limitation of our study.…”

Section: Discussionmentioning

confidence: 99%

The Quantitative Effect of Serum Albumin, Serum Urea, and Valproic Acid on Unbound Phenytoin Concentrations in Children

et al. 2013

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Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity.

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“…The free fraction was positively correlated with age in a study in healthy volunteers (Hooper et al 1974). In a comparison of the average percentage free phenytoin in groups of elderly and young subjects, the percentage free was significantly higher in elderly epileptic patients (12.8%) than in young patients (11.1%) [Patterson et al 1982;fig. 4].…”

Section: Antibacterialsmentioning

confidence: 97%

Plasma Protein Binding of Drugs in the Elderly

Wallace

Verbeeck

1987

Clinical Pharmacokinetics

121

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Binding to plasma proteins can affect the pharmacokinetics and pharmacodynamics of drugs. Age is one of many factors which can affect plasma protein binding of drugs. Unfortunately, very few generalities can be drawn from the studies of the effect of age on protein binding. Whether age has an effect on protein binding is dependent not only on the drug, but also on the manner in which the study is conducted. Several studies involve patients with various disease states making assessment of the effect of age alone on protein binding difficult. Results of different studies on the same drug do not always agree--in one case finding no change in protein binding with age and in another, a significant increase or decrease in protein binding. Most drugs which exhibit increased binding (decreased free fraction) in elderly subjects are basic and tend to have a greater affinity for alpha 1-acid glycoprotein than for albumin. The list of drugs exhibiting decreased binding (increased free fraction) in the elderly is longer and includes both acidic and basic drugs. The impact of changes in protein binding with age is dependent on the magnitude of the change, on the pharmacokinetic characteristics of the drug and on its therapeutic index. Some changes, although statistically significant, are not likely to be of importance clinically. From the studies reviewed, the free fraction is changed by greater than 50% in the elderly for only a few drugs, e.g. acetazolamide, diflunisal, etomidate, naproxen, salicylate, valproate and zimeldine.

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Plasma protein binding of phenytoin in the aged: in vivo studies.

Cited by 37 publications

References 13 publications

Variability of total phenytoin serum concentrations within elderly nursing home residents

Variability of total phenytoin serum concentrations within elderly nursing home residents

The Quantitative Effect of Serum Albumin, Serum Urea, and Valproic Acid on Unbound Phenytoin Concentrations in Children

Plasma Protein Binding of Drugs in the Elderly

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