Phenytoin Dose Adjustment in Epileptic Patients

Mawer, G. E.; Mullen, Peter W.; Rodgers, M.; Robins, Alexander; Lucas, S. B.

doi:10.1111/j.1365-2125.1974.tb00226.x

Cited by 60 publications

(14 citation statements)

References 5 publications

(13 reference statements)

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“…The dose at which enzyme saturation occurs was shown to vary considerably between patients by Mawer, Mullen, Rodgers, Robins & Lucas (1974), who successfully used the integrated form of the Michaelis-Menten equation described by Gerber & Wagner (1972) …”

Section: Discussionmentioning

confidence: 99%

Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

Houghton¹,

Richens²,

Leighton³

1975

Brit J Clinical Pharma

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1Steady-state serum phenytoin concentrations were measured in adult epileptic patients receiving a maintenance dose of phenytoin (300 mg daily). 2 Serum phenytoin concentration showed a positive correlation with age. 3 Serum phenytoin concentration showed a negative correlation with body weight and with height. Multiple correlation analysis indicated that body weight influenced the concentration to a much greater degree than height. 4 When corrected for body weight and height, the serum phenytoin concentrations in women were lower than those in men, although the difference was not statistically significant. 5 Although each of these factors contributes to the interindividual variation in serum phenytoin concentrations, the contribution of each is small. Other factors, such as genetic differences and the' effect of saturation kinetics, are much more important in determining steady-state concentrations. Adjusting the dose according to the age, weight and height of a patient would achieve only a marginal improvement in therapy.

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Section: Discussionmentioning

confidence: 99%

Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

Houghton¹,

Richens²,

Leighton³

1975

Brit J Clinical Pharma

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“…Although the correlation of an apparent Km estimated using isolated organelles with a 'Ki' determined from patient data must be viewed with caution, these values are of the same order of magnitude. The parameters calculated for our patients may be compared with a 'Km' of 26.8 iumol/1 and a 'Vmax' of 1 ytmol/l/hour determined by Gerber and Wagner (1972) for a single subject and with the mean values of a 'Km' of 15.1 ptmol/l and 'Vmax' 1.36 pmol/l/hour determined by Mawer et al (1974) from 15 patients. Kutt and Verebely (1970) found that diazepam inhibited phenytoin metabolism by rat liver microsomes in vitro.…”

Section: Discussionmentioning

confidence: 80%

Phenytoin intoxication during concurrent diazepam therapy

Rogers

Haslam

Longstreth

et al. 1977

Journal of Neurology, Neurosurgery & Psychiatry

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Phenytoin possesses a relatively small therapeutic index, and toxicity is by no means uncommon during therapy making monitoring of plasma levels an important adjunct to clinical management (Dawson and Jamieson, 1971). This situation is further complicated by the non-linear relationship between dose and the resulting plasma concentration (Bochner et al., 1972). The apparent half-life of the drug increases as the plasma level rises, phenytoin elimination being described as dose-dependent. This type of elimination can be described as obeying Michaelis-Menten kinetics overall (Gerber and Wagner, 1972). It follows from these kinetic properties that the relationship of plasma levels to dose is non-linear, and that at higher plasma levels a small increase in dose produces a disproportionately large increase in plasma levels. The Institute for evaluation and the dose of phenytoin increased to 9 mg/kg/day which resulted in levels of 36 ,tmol/l. Diazepam was added (for spasticity) in a dose of 0.3 mg/kg/day and increased by increments of 0.1 mg/kg/day at intervals of approximately five days to 0.6 mg/kg/day. Simultaneously the phenytoin dose was increased to 12.5 mg/kg/ day. Fourteen days after the addition of diazepam and the increased dose of phenytoin the patient experienced phenytoin toxicity characterised by 890

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“…Mawer, Mullen, Rodgers, Robins & Lucas (1974) observed a mean fall from 12.5 to 7.5 Ag/ml over a 24 h period in fifteen patients. Many other authors have made similar observations.…”

Section: Introduction Methodsmentioning

confidence: 91%

Control of epilepsy with a single daily dose of phenytoin sodium.

Cocks¹,

Critchley²

1975

Brit J Clinical Pharma

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Fifty‐three patients in an epileptic centre have been studied. All were receiving phenytoin and many were also receiving other antoconvulsant drugs. 2. Thirty‐six patients took part in a three month cross over study. There was no significant change in the frequency of epileptic seizures or in the late morning serum concentration of phenytoin when the treatemtn was changed from two to three spaced doses of phenytoin sodium/day to a single dose at 12.00 hours. 3. Seventeen patients acted as a control group. They received phenytoin sodium as two or three spaced doses/day throughout the study. There was no significant change in the frequency of epileptic seizures or in the late morning serum concentration of phenytoin between the first and second three month periods of observation. 4. It is concluded that the total daily dose of phenytoin sodium may be given once daily without reduction of the anticonvulsant effect.

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Phenytoin Dose Adjustment in Epileptic Patients

Cited by 60 publications

References 5 publications

Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

Phenytoin intoxication during concurrent diazepam therapy

Control of epilepsy with a single daily dose of phenytoin sodium.

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