A Longitudinal Study of Valproate Free Fraction in the Specific Age Group at Greatest Risk for Febrile Convulsions (Children Below 3 Years)

Monaco, Francesco; Mele, G.; Meloni, T; Sotgia, A.; Mutani, Roberto

doi:10.1111/j.1528-1157.1984.tb04182.x

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The eruption can vary from slight scaling and minimal redness to generalized desquamation associated with systemic toxic symptoms [1]. Sodium valproate is being used for febrile convulsions with no particular toxic effect in young children [2]. We are reporting a case of recurrent febrile convulsions who was put on long term anticonvulsive therapy, sodium valproate, and developed one of the rare complications, exfoliative dermatitis, with this drug.…”

Section: G Nabi Exfoliative Dermatitis (Sodium Valproate Induced) 1mentioning

confidence: 99%

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Exfoliative Dermatitis (Sodium Valproate Induced)

Nabi¹

1993

Ann Saudi Med

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G Nabi, Exfoliative Dermatitis (Sodium Valproate Induced). 1993; 13(4): 388-389To the Editor: Exfoliative dermatitis is an erythematous scaling eruption which involves most or all of the skin. The eruption can vary from slight scaling and minimal redness to generalized desquamation associated with systemic toxic symptoms [1]. Sodium valproate is being used for febrile convulsions with no particular toxic effect in young children [2]. We are reporting a case of recurrent febrile convulsions who was put on long term anticonvulsive therapy, sodium valproate, and developed one of the rare complications, exfoliative dermatitis, with this drug.A two-year-old Sudanese male presented with a history of recurrent convulsions since the age of nine months. He had five attacks of convulsions until he reported to our clinic. Each attack lasted from three to five minutes, tonic clonic type, always associated with respiratory tract infection and fever. The patient was getting the treatment for each episode from the local dispensary, syrup ampicillin and paracetamol. Antenatal, natal, and postnatal history were uneventful. There was no family history of convulsions or skin disease. On examination, the patient was of average build and undernourished; growth parameters were a weight of 10 kg (below the tenth percentile), length 85 cm and head circumference 48 cm, both normal. Vital signs were within normal limits. There was no neurological deficit and all other systems were clinically normal. Investigations: hemoglobin, total leucocyte count, total proteins, serum electrolytes, blood glucose, blood gases, x-ray of the skull, electroencephalography, and liver function tests were all normal. The patient was put on long term anticonvulsive therapy of Depakine syrup (sodium valproate) 20 mg/kg/day in two divided doses per oral for a period of two years.Six weeks after starting the treatment, he developed generalized redness of the skin with itching all over the body. The erythema was a bright red, classical allergic drug rash. The patient was taking only Depakine and no other medication. There was no fever, jaundice, lymphadenopathy, hepatosplenomegaly, or signs of congestive cardiac failure. The drug was stopped and the patient was put on chlorpheniramine maleate syrup 0.35 mg/kg/day in three divided doses per oral. Local application of calamine lotion was used as a soothing agent. Itching subsided and desquamation started; this lasted for a period of two weeks. In a total period of one month, skin was normal and the child was healthy. He is coming for follow-up regularly.Sodium valproate is a widely used drug for febrile convulsions. Usually in therapeutic doses, there are minimal side effects [2]. One of the rare complications of this drug is hepatotoxicity (one per 10,000 patients) [3]. Idiosyncrasy has been reported in some cases but exfoliative dermatitis due to this drug is very rare [4]. Exfoliative dermatitis is more common in adults than in children and males are affected more than females [5]. The patient developed skin ras...

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Section: G Nabi Exfoliative Dermatitis (Sodium Valproate Induced) 1mentioning

confidence: 99%

“…Usually in therapeutic doses, there are minimal side effects [2]. One of the rare complications of this drug is hepatotoxicity (one per 10,000 patients) [3].…”

Section: G Nabi Exfoliative Dermatitis (Sodium Valproate Induced) 1mentioning

confidence: 99%

Exfoliative Dermatitis (Sodium Valproate Induced)

Nabi¹

1993

Ann Saudi Med

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Assessment of Drug Concentrations in Tears in Therapeutic Drug Monitoring: I. Determination of Valproic Acid in Tears by Gas Chromatography/Mass Spectrometry With EC/NCI Mode

Nakajima¹,

Yamato²,

Shimada³

et al. 2000

Therapeutic Drug Monitoring

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A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the biologic fluid. The concentrations in tears [C]t correlated very well with those of the free form in the plasma [Cf]p and those of the total form in the plasma [Cb+f]p. The ratios between valproic acid concentrations in tears and plasma were as follows: [C]t/[Cb+f]p = 0.10 +/- 0.02; [C]t/[Cf]p = 0.57 +/- 0.11. Ratios of [C]t/[Cb+f]p were in good agreement with previously published data.

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Clinical Pharmacokinetics of Antiepileptic Drugs in Paediatric Patients

Battino

Estienne

Avanzini

1995

Clinical Pharmacokinetics

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This article reviews 119 papers published since 1964 on the pharmacokinetics of phenobarbital, primidone, valproic acid, ethosuximide and mesuximide (methsuximide) in paediatric patients. Particular attention has been paid to the role of age in determining the variability of pharmacokinetic parameters, but the effect of other factors, such as different formulations and routes of administration, concomitant treatments, gender and pathological conditions other than epilepsy, have also been considered. Mean phenobarbital terminal half-life (t1/2z) is very long in neonates (45 to 409 hours) and decreases with age. Therefore, a low dose per kilogram (dose/kg) is recommended during the neonatal period. The dose requirement decreases with increasing age, especially in children also taking valproic acid, which inhibits phenobarbital metabolism. Primidone is metabolised to phenobarbital and phenylethylmalonilamide; the metabolic conversion rate is increased by enzyme-inducing drugs and inversely correlated with age, being virtually absent in neonates. Valproic acid is extensively bound to plasma proteins, but there is a high interindividual and intraindividual diurnal variability in the binding, which depends on the concentration of binding proteins (i.e. albumin) and binding modulators (e.g. free fatty acids) but not on age (at least in those patients aged between 3 months and 65 years). The clearance (CL/F) of valproic acid positively correlates with the unbound concentrations and is strongly age-dependent, being low in neonates and high at the end of the first postnatal month, and progressively decreasing from 2 months to 14 years. The combination of these factors leads to a very poor correlation between plasma concentrations and dose/kg (C/D) and between plasma concentrations of total valproic acid and efficacy. Children also taking enzyme-inducing antiepileptic drugs require a larger valproic acid dose/kg, whereas the coadministration of aspirin (acetylsalicylic acid) may decrease the clearance of unbound drug (CLu/F), and thus require a decrease in the daily dose of valproic acid. Ethosuximide is well absorbed, minimally protein bound and slowly eliminated. Lower C/D ratios are reported in children younger than 10 years old than in older children and in individuals also taking enzyme-inducing drugs (i.e. primidone). According to the only available paper on mesuximide in paediatric patients, the C/D ratio is less sensitive to both age and associated therapy.

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A Longitudinal Study of Valproate Free Fraction in the Specific Age Group at Greatest Risk for Febrile Convulsions (Children Below 3 Years)

Cited by 3 publications

References 6 publications

Exfoliative Dermatitis (Sodium Valproate Induced)

Exfoliative Dermatitis (Sodium Valproate Induced)

Assessment of Drug Concentrations in Tears in Therapeutic Drug Monitoring: I. Determination of Valproic Acid in Tears by Gas Chromatography/Mass Spectrometry With EC/NCI Mode

Clinical Pharmacokinetics of Antiepileptic Drugs in Paediatric Patients

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