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Journal ArticleDOI

Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution.

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TLDR
Plasma protein binding of diphenylhydantoin (DPH) in normal plasma was investigated with an ultrafiltration technique (at room temperature) with the use of 14C‐labeled DPH with no marked difference between sexes or individuals.
Abstract
Plasma protein binding of diphenylhydantoin (DPH) in normal plasma was investigated with an ultrafiltration technique (at room temperature) with the use of 14C-labeled DPH. DPH was 92.6 per cent bound. There was no marked difference between sexes or individuals. In blood donor plasma the bound fraction was 93 per cent at a concentration of DPH of 16 μg per milliliter (therapeutic concentration). The binding was less at 37° C. than at wom temperature. The effect on DPH binding of some other drugs, including various anti-epileptics, was investigated. Of these only salicylic acid, sulfafurazole and phenylbutazone (in concentrations which may be obtained clinically) decreased DPH binding. The effects of plasma dilution and of dilution of both plasma and DPH were investigated. In the former case unbound concentrations increased but were fairly constant in the latter. The clinical significance of these findings is discussed.

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Citations
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Journal ArticleDOI

Decreased plasma protein binding of phenytoin in patients on valproic acid.

TL;DR: It is concluded that patients on combined treatment with phenytoin and valproic acid have an unpredictably raised free fraction of pheny toin and this drug interaction can complicate the important plasma level monitoring of phenYtoin in epileptic patients unless the free concentration of this drug can be analysed or estimated.
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Phenytoin-salicylate interaction.

TL;DR: Serum total phenytoin concentration may fall during salicylate therapy but the dose of pheny Toin should not be altered unless there are overt signs of toxicity, and the rise (16%) in the free (salivary) pheny toin concentration was small.
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Use of antiepileptic drugs in hepatic and renal disease.

TL;DR: The use of antiepileptic drugs in the presence of hepatic or renal disease is complex and requires great familiarity with the pharmacokinetics of these agents.
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Interactions with antiepileptic drugs.

TL;DR: Most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective.
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Plasma protein binding of phenytoin after cholecystectomy and neurosurgical operations

TL;DR: It was found that the fraction of pheny toin not bound to plasma proteins rose significantly after operation, and the total concentration decreased, so the concentration of free phenytoin did not change much.
References
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Journal ArticleDOI

Clinical and electroencephalographic correlations with serum levels of diphenylhydanotin.

TL;DR: The correlation is described between the serum level of diphenylhydantoin and the anticonvulsant effect of the drug, the incidence of paroxysmal abnormalities in the electroencephalogram, and the occurrence of toxic side-effects.
Journal ArticleDOI

Diphenylhydantoin Metabolism, Blood Levels, and Toxicity

TL;DR: Detailed data have been obtained relating symptoms and signs of toxicity to blood levels of diphenylhydantoin relating to the common signs of dose-related toxicity and defects in the metabolism of DiphenylHydantoin.
Journal ArticleDOI

Clinical pharmacology of the new penicillins: I. The importance of serum protein binding in determining antimicrobial activity and concentration in serum

TL;DR: In vitro studies comparing minimal inhibitory and bactericidal activity of these penicillins in 100 per cent human serum and trypticase soy broth revealed a close relation of inhibition of antimicrobial action to the extent of binding to serum.
Journal ArticleDOI

Metabolic disposition of diphenylhydantoin in normal human subiects following intravenous administration

TL;DR: The maximum excretion rate of HPPH was found to occur about 6 to 8 hours after the intravenous dose, presumably due to an initial delay in the enzymatic processes of hydroxylation or conjugation prior to excretion of the metabolite.
Journal ArticleDOI

Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinemic infants

TL;DR: The plasma protein binding of diphenylhydantoin (DPH) in heparinized plasma from normal and hyperbilirubinemic newborn infants was investigated by means of an ultrafiltration technique utilizing 14 C-DPH.
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