Biomaterial Database

Fluctuations of unbound and total phenytoin concentrations during the day in epileptic patients on valproic acid comedication. 1990

T May, and B Rambeck

Department of Biochemistry, Gesellschaft für Epilepsieforschung, Bielefeld-Bethel, F.R.G.

The influence of daily fluctuations in the concentration of valproic acid (VPA) on the unbound and total concentration of phenytoin (PT) was examined in a prospective study. The serum concentrations of 28 patients with epilepsy (group PT + VPA) who were treated with PT and concurrently with VPA and 15 patients (group PT) who were treated with PT but without VPA comedication were determined at 8.00, 11.00, 14.00, 17.00, and in part at 20.00 h. The results show that there are significantly greater fluctuations in the total PT concentration among patients on VPA than those not on VPA. The fluctuations in the total PT concentration during the day correlated with the fluctuations in the VPA concentration. On the other hand, the fluctuations in the concentrations of unbound PT of patients on VPA were comparable with those not on VPA. In the absence of VPA, the diurnal fluctuations of the total PT concentration correlated highly significantly with the fluctuations of the unbound PT concentration. This is not the case in patients on VPA. Our data are a further indication of the smaller significance of the total PT concentration as compared with the unbound PT concentration in the combined treatment of PT and VPA.

UI	MeSH Term	Description	Entries
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
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
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
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
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D014635	Valproic Acid	A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.	Dipropyl Acetate,Divalproex,Sodium Valproate,2-Propylpentanoic Acid,Calcium Valproate,Convulsofin,Depakene,Depakine,Depakote,Divalproex Sodium,Ergenyl,Magnesium Valproate,Propylisopropylacetic Acid,Semisodium Valproate,Valproate,Valproate Calcium,Valproate Sodium,Valproic Acid, Sodium Salt (2:1),Vupral,2 Propylpentanoic Acid