Plasma concentrations of valproate during maintenance therapy in epileptic children. 1982

B Lundberg, and A Nergårdh, and L O Boréus

A total of 20 children with various types of epilepsy were treated with valproate, 11 with monotherapy and 9 with valproate in combination with phenobarbitone, phenytoin, or carbamazepine. Valproate was given either every 8 or 12 h. At least two different dose levels were tried in each patient. The pharmacokinetics of valproate during the interval between doses was determined using a gas chromatographic technique. The clinical effect of the treatment was assessed by interviewing the parents. The plasma concentrations showed considerable fluctuation during the intervals between doses. The mean increase from pre-administration to peak level was 82% when the dose interval was 12 h, and 62% when it was 8 h. The mean plasma half-life of valproate, using a one-compartment model, was 10.9 +/- 1.3 h (mean +/- SD). The plasma half-life of valproate was decreased when the drug was combined with the other anti-epileptics. The calculated area under the concentration versus time curve was linearly related to dose, both in a single patient on four dose levels and when different patients were compared. The clinical effect of valproate monotherapy was best in patients with absences, usually good in myoclonus and less favourable in other types of epilepsy. For children with absences, the optimal dose range of valproate was between 20 and 40 mg/kg/24 h. In comparison, the myoclonic types of epilepsy needed a slightly higher dose level, between 30 and 60 mg/kg/24 h. In the latter group a "therapeutic window" seems to exist, since patients below and above the suggested dose levels were not well-controlled. Therapeutic monitoring of valproate does not appear meaningful when the drug is used as monotherapy. However, in combination therapy, determination of the plasma levels of all anti-convulsants used may be helpful. The large fluctuations of valproate during a dose interval must be taken into consideration when the clinical effects are analysed.

UI MeSH Term Description Entries
D008297 Male Males
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D004832 Epilepsy, Absence A seizure disorder usually occurring in childhood characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736) Akinetic Petit Mal,Epilepsy, Minor,Petit Mal Epilepsy,Pyknolepsy,Absence Seizure Disorder,Childhood Absence Epilepsy,Epilepsy Juvenile Absence,Epilepsy, Absence, Atypical,Epilepsy, Petit Mal,Juvenile Absence Epilepsy,Pykno-Epilepsy,Seizure Disorder, Absence,Absence Epilepsy,Absence Epilepsy, Childhood,Absence Epilepsy, Juvenile,Absence Seizure Disorders,Epilepsy, Childhood Absence,Epilepsy, Juvenile Absence,Minor Epilepsy,Petit Mal, Akinetic,Pykno Epilepsy,Pyknolepsies,Seizure Disorders, Absence
D005260 Female Females

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