[Bioavailability of phenytoin. Comparison of data obtained in vitro, in healthy volunteers and in epileptic patients].
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Adolescent↗
Biomedical subjects
A Baruzzi
Publications and source records attributed to A Baruzzi.
[Relative bioavailability of phenytoin and barbiturates in single or combined preparations].
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Barbiturates↗
Rapid quantitative determination of underivatized carbamazepine, phenytoin, phenobarbital and p-hydroxyphenobarbital in biological fluids by packed column gas chromatography.
A method is described for measuring, without derivatization, the concentrations of phenobarbital, p-hydroxyphenobarbital, carbamazepine and phenytoin in biological fluids of epileptic patients undergoing long-term therapy. This method uses, at an isothermal temperature, a special column packing (GP-2% SP-2510-DA on 100-120 mesh Supelcoport). The lower limit of detection for all substances analyzed is 1 microgram/ml of biological material. The recovery of the compounds is about 95%, the reproducibility of the method is good (coefficient of variation, 4.3%). The mass spectra confirm the identity of substances eluting from the column. There is no interference from other commonly used antiepileptic drugs or endogenous substances. The method has the advantages of high specificity, sensitivity and rapidity and it appears to be suitable for the routine monitoring of blood and urine concentrations in patients receiving multi-drug therapy.
Adult↗
Cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid in hypersomnia with periodic apneas or idiopathic hypersomnia: preliminary results.
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Aged↗
Antiepileptic drug therapy and plasma levels in 2500 patients from Northern Italy.
The antiepileptic drug therapy of 1912 patients coming from various neurological clinics of Northern Italy has been evaluated in a collaborative survey. The following epidemiological data have been analysed: incidence of the various seizures types, according to the International Classification (Gastaut, 1969), in relation to the age; drug choice and therapeutic schedules in relation to the seizure type and to the age; number of drugs administered in various age and seizure groups; side effects in relation to type, number and plasma concentrations of the administered drugs. The analysis of the drug plasma level determinations, carried out either with gas-chromatographic methods or with the EMIT system, was effected in order to evaluate the number of patients who were under, in or over the suggested therapeutic ranges, the influence of age on drug disposition and the modifications of the drug plasma levels due to drug interactions.
Adolescent↗
A month-by-month long-term study on carbamazepine:clinical, EEG and pharmacological evaluation.
Carbamazephine plasma levels were monitored for a twelve-month period in twenty epileptic patients. Seizure frequency decreased remarkably on inclusion of the drug in the therapy and attainment of plasma levels of 7-9 microgram/ml. A faster breakdown rate in children was confirmed, while carbamazepine-10, 11-epoxide was present for carbamazepine levels above 4-5 microgram/ml. EEG tracings did not show substantial modifications; this variable was thus considered to be of little value in assessing the clinical picture. Side-effects were minimal. Carbamazepine is increasingly becoming the drug of first choice in the management of both generalized and partial epilepsy, while better and more rapid results are obtained in monotherapy.
Adolescent↗
Carbamazepine and carbamazepine-10, 11-epoxide concentrations in human brain.
1 Carbamazepine (CBZ) brain and plasma concentrations were measured in twenty-one patients undergoing brain surgery for tumour removal. The drug was administered prophylactically at doses ranging from 6.9 to 14.8 mg/kg for 4-5 days before the intervention. 2 In seventeen cases where sample were collected 10-14 h after dosing, CBZ brain levels ranged from 2.2-14.5 microgram/g. A significant linear relationship (p less than 0.01) was observed between brain and plasma concentrations with a brain/plasma ratio of 1.1 +/- 0.1. 3 Carbamazepine 10,11-epoxide (CBZ-Epox), present in all samples, could be quantified in three brain specimens. Its brain concentrations ranged from 1.5-2.7 microgram/g with a brain/plasma ratio of 1.1-1.2. 4 Parieto-occipital areas tended to show higher CBZ concentrations while lower values were found in temporal regions. Very low CBZ levels were found in two gliomas while in meningiomas CBZ levels were similar to those observed in normal tissue. 5 The data, showing a linear relationship between brain and plasma concentrations of both CBZ and its epoxide, give additional significance to the plasma level monitoring of antiepileptic drugs.
Adult↗
Phenytoin encephalopathy as probable idiosyncratic reaction: case report.
A case of phenytoin (DPH) encephalopathy with increasing seizures and EEG and mental changes is described. Despite adequate oral dosage of DPH (5 mg/kg/daily) the plasma level was very low (2.8 microgramg/ml). The encephalopathy was probably an idiosyncratic and not toxic or allergic reaction. In fact the concentration of free DPH was normal, the patient presented a retarded morbilliform rash during DPH treatment, the protidogram was normal, and an intradermic DPH injection had no local effect. The authors conclude that in a patient starting DPH treatment an unexpected increase in seizures, with EEG and mental changes occurring simultaneously, should alert the physician to the possible need for eliminating DPH from the therapeutic regimen, even if plasma concentrations are low.
Adult↗
Plasma levels of di-no-propylacetate and clonazepam in epileptic patients.
Plasma levels of DPA and CNP and associated antiepileptic drugs were measured in groups of respectively 106 and 30 epileptic patients aged from 3 to 49 years. A poor correlation between daily oral dose and plasma levels of both drug was observed when the whole group of patients was considered. A better correlation was seen in a group of adult patients who received DPA and PB. Children below 10 years of age disposed both drugs faster than adults and the difference was significant (p less than 0.01) in groups receiving PB as associated drug. Patients medicated with PB and DPA or CNP showed lower plasma levels of both drugs; on the other hand DPA appeared to cause a decrease of PB clearance which was more marked in children. The clinical significance of the fluctuations of daily plasma levels of both drugs are discussed in relationship to the schedule of administration and plasma sampling. Observations on the therapeutic ranges and adverse effect of the drugs are reported.
Adolescent↗
Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy.
A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin. Two population-based dosing methods (population clearance method and bayesian feedback method) and one individual-based method (the so-called linearized Michaelis-Menten method) were evaluated, when applicable, for single-point and/or 2-point dose predictions of phenytoin. In single-point predictions, we found a generally low percentage of dose calculations falling inside the +/- 10% range (48.9% and 51.1% for the population clearance and the bayesian methods, respectively). In 2-point predictions, the bayesian method was 'accurate' (dose within the +/- 10% range) in approximately 54.3% or 55.0% of cases (depending on the particular method of implementation adopted). An even worse percentage of 'accurate' dose predictions (38.3%) was obtained by using the linearized Michaelis-Menten method. Our data do not confirm results from previous studies indicating a generally good performance of pharmacokinetic methods for predicting phenytoin dosage.
Adolescent↗
Free and total serum concentrations of carbamazepine and carbamazepine-10,11-epoxide in infancy and childhood.
Total and free serum concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) at steady state were determined in 10 infants (ages 4-13 months), 10 preschool children (ages 3-5 years), and 11 school children (ages 7-11 years) receiving equivalent doses of CBZ alone. Free and total CBZ levels tended to increase with increasing age, while CBZ-E levels did not show any significant age dependency. As a result, CBZ-E/CBZ ratios were higher in infants and preschool children than in the older age group. The degree of plasma protein binding of CBZ and CBZ-E did not show any important differences among the various groups. These data provide evidence that, within a pediatric population, CBZ shows age-related dispositional changes which may be clinically important.
Age Factors↗
Clobazam in therapy-resistant patients with partial epilepsy: a double-blind placebo-controlled crossover study.
Clobazam was compared with placebo as antiepileptic adjunct medication in 129 therapy-resistant epileptic patients who were mainly suffering from complex partial seizures. The study was performed in five European countries according to a double-blind crossover design lasting 7 months. Two treatment periods of 3 months (1 month adjustment and 2 months maintenance medication) were separated by one medication switch-over month. The difference in seizure reduction between clobazam and placebo was significant (p less than 0.05). Nineteen percent of patients receiving clobazam became seizure-free during the maintenance dose period. In contrast, freedom from seizures was not observed in any placebo patient. Electroencephalogram (EEG) signs, mood ratings, and global impressions also indicated therapeutic effects of clobazam in epilepsy. The most frequent adverse reactions to clobazam were drowsiness and dizziness. However, the sedative effects of clobazam seemed to be less pronounced in comparison with other benzodiazepines. The study gives evidence of the therapeutic value of clobazam as adjunct medication in therapy-resistant partial seizures. The use of clobazam as monotherapy and long-term treatment, as well as the particular seizure response pattern to clobazam, has to be further investigated.
Adult↗
Safety of valproate in porphyria cutanea tarda.
Treatment of epileptic seizures in patients with hepatic porphyrias is a challenging problem due to enzymatic induction activity of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and clonazepam (CZP). We present the case of a patient with partial seizures treated with PHT and showing clinical signs and biochemical abnormalities of porphyria cutanea tarda (PCT). We withdrew PHT and treated the patient with sodium valproate (VPA). We followed the patient for 6 months during VPA therapy. During this period, clinical signs of PCT disappeared and biochemical values normalized. Our study shows that VPA is a safe treatment in epileptic patients with PCT.
Aged↗
Neuroocular side effects of carbamazepine and phenobarbital in epileptic patients as measured by saccadic eye movements analysis.
The effect of carbamazepine (CBZ) and phenobarbital (PB), alone and in association, on the function of specific brain structures was studied in chronically treated epileptic patients by means of saccadic eye movements (SEMs) analysis. The relationship between daily fluctuations of CBZ plasma levels and the occurrence of intermittent side effects was also evaluated. All treatments produced a significant impairment (p less than 0.001) of SEM function as compared with a group of controls. SEM abnormalities appeared to change in relation to daily fluctuation of CBZ plasma levels. When the SEM parameters were considered separately, PB showed a significantly (p less than 0.001) more relevant sedative effect, whereas both drugs appear to produce the same effect on cerebellar and pontine functions. Although impairment of SEM function was most likely far from reaching clinical significance, it represents important information for the clinician.
Adult↗
Clarithromycin-carbamazepine interaction: a case report.
We report a clinically relevant interaction between a new macrolide antibiotic, clarithromycin, and carbamazepine (CBZ). In a patient receiving CBZ monotherapy, 10-day antibiotic treatment increased CBZ concentration despite concomitant CBZ dose reduction and doubled the CBZ concentration/dose ratio. Concentration of the CBZ epoxide (CBZ-E) metabolite was reduced, suggesting that the interaction occurs at a metabolic level.
Adult↗
Carnitine disposition before and during valproate therapy in patients with epilepsy.
Free and total carnitine and acylcarnitine in plasma and urine samples was measured in 22 epileptic patients before and after 15 and 45 days of valproate (VPA) therapy and in 16 healthy volunteers on a single occasion. Carnitine plasma concentration and renal excretion observed in epileptic patients before VPA therapy did not differ from control values. After VPA was started, free and total plasma concentration decreased significantly (p < 0.05) from 49 +/- 17 to 35 +/- 16 at 15 days and to 35 +/- 13 nmol/ml at 45 days of therapy (free carnitine) and from 60 +/- 18 to 50 +/- 18 at 15 days and to 55 +/- 14 nmol/ml at 45 days of therapy (total carnitine), whereas acylcarnitine increased significantly (p < 0.05) from 10 +/- 8 to 14 +/- 8 at 15 days and to 18 +/- 16 nmol/ml at 45 days of therapy. Free carnitine urinary excretion decreased significantly (p < 0.05) from 200 +/- 135 to 115 +/- 76 and 118 +/- 75 mumol/24 h, whereas acylcarnitine urinary excretion increased significantly (p < 0.05) from 78 +/- 56 to 154 +/- 98 and 155 +/- 89 mumol/24 h after VPA therapy was started. As a consequence, acylcarnitine renal clearance increased significantly (+30%, p < 0.05) whereas free carnitine renal clearance did not change during VPA therapy. No difference was detected between 15 and 45 days of therapy. No patients experienced symptoms of VPA toxicity. Our results suggest that VPA in patients increases both formation and renal clearance of acylcarnitine.
Acylation↗
Arylsulfatase A pseudodeficiency and Lafora bodies in a patient with progressive myoclonic epilepsy.
Since age 12 years, a 25-year-old woman had a syndrome with myoclonic epilepsy, cerebellar signs, and spontaneous myoclonus. Skin biopsy showed typical Lafora bodies (LB), but she lacked a progressive course and mental impairment, hallmarks of Lafora disease. Lysosomal enzyme assays showed low level arylsulfatase A (ASA) activity. DNA study disclosed a homozygous ASA Pd genotype. Both parents carried one Pd allele. The still-unknown relationship between the pathologic level of ASA activity and myoclonic epilepsies suggests introduction of ASA assays in patients with PME.
Adult↗
Free concentration of carbamazepine and carbamazepine-10,11-epoxide in children and adults. Influence of age and phenobarbitone co-medication.
Total and free plasma concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) were determined in 39 children (aged 3 to 10 years) and 79 adults (aged 15 to 65 years) receiving long term treatment with CBZ alone or in combination with phenobarbitone (PB). Compared with the corresponding age groups treated with CBZ alone, adults and children receiving PB co-medication showed lower total and free CBZ concentrations, similar CBZ-E concentrations and higher CBZ-E/CBZ ratios. Among patients on CBZ alone, children had at any given dose lower total and free CBZ and CBZ-E concentrations than adults. Lower CBZ levels in children than in adults were also found among patients receiving phenobarbitone in combination. CBZ-E/CBZ ratios did not differ significantly between children and adults. These data provide evidence that children show an elevated free CBZ clearance with a metabolic pattern different from that observed during phenobarbitone induction.
Adult↗