The effects of salicylate on the pharmacokinetics of phenytoin

Olanow, C. Warren; Finn, Arthur L.; Pharm, D; Prussak, Charles

doi:10.1212/wnl.31.3.341

Cited by 13 publications

(5 citation statements)

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“…One patient had a seizure coincident with the introduction of amitriptyline, which is epileptogenic in therapeutic doses. 15 One patient had signs of phenytoin toxicity (drowsiness, ataxia) associated with plasma phenytoin concentrations of only 50-60 !Jmol/1; it was considered that aspirin (4 g daily), which displaces phenytoin from plasma proteins, 16 may have resulted in phenytoin toxicity, with resulting increased likelihood of seizures. 17 Subjects were questioned on factors which they considered were involved in causing the attack for which the ambulance was called.…”

Section: Resultsmentioning

confidence: 99%

Factors Which Influence the Effectiveness of Treatment of Epilepsy

Lambie

Stanaway

Johnson

1986

Australian and New Zealand Journal of Medicine

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Despite recent advances in the management of epilepsy, some patients continue to have seizures which defy therapeutic intervention. To examine factors which may influence the successful application of therapy a survey was carried out of 103 patients, with a previous diagnosis of epilepsy, who had a seizure for which an ambulance was called. It was evident that anticonvulsants are not always used to their maximum potential or under optimal conditions. Problems which were identified in treatment included the widespread use of polypharmacy. Patients contributed to failure of seizure control by lack of compliance with therapy (29 patients) and by excessive alcohol consumption (19 patients).

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Section: Resultsmentioning

confidence: 99%

Factors Which Influence the Effectiveness of Treatment of Epilepsy

Lambie

Stanaway

Johnson

1986

Australian and New Zealand Journal of Medicine

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“…Both aspirin and salicylic acid have been shown to displace phenytoin from plasma protein binding sites in vitro (Odar-CederlOf and Borga, 1976;Porter and Layzer, 1975) and in vivo (Fraser et al, 1980;Leonard et al, 1981;Olanow et al, 1981;Paxton, 1980). The in vivo studies have demonstrated that relatively large doses of either anti-inflammatory agent cause a fall in total serum phenytoin levels, with little or no change in free phenytoin concentration.…”

Section: Aspirin and Salicylic Acidmentioning

confidence: 99%

Pharmacokinetic Interactions with Antiepileptic Drugs

Perucca

1982

Clinical Pharmacokinetics

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A large number of pharmacokinetic interactions with antiepileptic drugs have been reported in recent years. Among the interactions affecting the disposition of anticonvulsants, the most important are probably those resulting in inhibition of the metabolism of phenytoin, phenobarbitone and carbamazepine. Drugs which have been shown to inhibit the metabolism of these anticonvulsants and to precipitate clinical signs of intoxication in epileptic patients include sulthiame, valproic acid, chloramphenicol, certain sulphonamides, phenylbutazone, isoniazid and propoxyphene. Interactions affecting the plasma protein binding of antiepileptic drugs are less likely to cause long-lasting alterations in response, but they are important because they change the relationship between serum drug concentrations and clinical effect. Anticonvulsant agents may induce important alterations in the pharmacokinetics of other drugs. Phenytoin and phenobarbitone may decrease the gastrointestinal absorption of frusemide and griseofulvin, respectively. Many of the drugs used in the treatment of the adult epilepsies, including phenytoin, phenobarbitone, primidone and carbamazepine, are potent inducers of the hepatic microsomal enzymes. This results in an increased rate of metabolism and decreased clinical efficacy of a number of drugs, including dicoumarol, steroid oral contraceptives, metyrapone, glucocorticoid agents, doxycycline, quinidine and vitamin D.

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“…The use of this measurement assumes that protein and has low hepatic clearance there is little interindividual variability in plasma (Wilkinson & Shand, 1975;Borga, 1980;Levy, protein binding of the drug, which is not 1980). It is now clearly recognised that the protein binding of phenytoin is reduced with *Present address: Department of Pharmacology, impaired renal function (Reidenberg etal., 1971), Faculty of Science, Prince of Songkla University, low plasma albumin concentration (Hooper et Haad- Yai, Thailand al., 1974), in pregnancy (Perucca etal., 1981) and 539 in neonates (Fredholm et al, 1975), and in the presence of displacing drugs such as sodium valproate (Perucca et al, 1980) and high dose aspirin (Leonard et al, 1981;Olanow et al, 1981). This is not an exclusive list as other unidentified factors may also alter phenytoin protein binding.…”

Section: Introductionmentioning

confidence: 99%

Plasma concentrations of unbound phenytoin in the management of epilepsy.

Kilpatrick¹,

Wanwimolruk²,

Wing³

1984

Brit J Clinical Pharma

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1 In 46 epileptic patients the range of the unbound fraction of phenytoin in plasma measured by ultrafiltration (at 37°C) and tracer-labelling with [I4C]-phenytoin was 6.7%-33.3% with a median of 11.9%. 2 The total and unbound phenytoin plasma concentrations were significantly correlated (r = 0.93, P < 0.001), but in six patients the unbound concentration fell on or outside the 90% predictability limits for a single value. In all patients the unbound concentration reflected the clinical status of the patient equally or better than the total concentration. 3 An inverse relationship was found between the plasma albumin concentration (within the normal reference range) and the phenytoin unbound fraction (r = -0.83, P < 0.001) indicating that plasma albumin concentration is one of the important overall determinants of phenytoin protein binding. 4 Saliva and plasma unbound phenytoin concentrations were significantly correlated (r = 0.98, P < 0.001) but both collection of plasma samples and preparation of plasma ultrafiltrate using the Amicon micropartition system are simpler than collection and processing saliva, and interpretation of plasma unbound concentration does not require allowance for potential contamination. 5 The additional value of the unbound phenytoin concentration in a clinically significant number of individuals would justify routine measurement of unbound phenytoin concentration in monitoring therapy, once available simplified methodology has been adequately characterised.

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The effects of salicylate on the pharmacokinetics of phenytoin

Cited by 13 publications

References 0 publications

Factors Which Influence the Effectiveness of Treatment of Epilepsy

Factors Which Influence the Effectiveness of Treatment of Epilepsy

Pharmacokinetic Interactions with Antiepileptic Drugs

Plasma concentrations of unbound phenytoin in the management of epilepsy.

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