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Results for “Ethosuximide”

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At least 19 recordsLinked to original sources

PubMed1978

Ethosuximide pharmacokinetics in a pregnant patient and her newborn.

Ethosuximide concentration in serum was monitored during the last trimester of pregnancy in a patient. After delivery, the decline in serum concentration of ethosuximide was observed in the nonnursing neonate. The half-life of elimination of transplacentally acquired ethosuximide in this neonate was 41.3 hr. The ratio of breast milk to maternal serum concentration of ethosuximide was approximately 1. A total daily exposure to ethosuximide of 12.8 to 38.4 mg (3.6 to 11.0 mg/kg) as a result of nursing was predicted.

Adult↗

PubMed1975

The effect of phenytoin and ethosuximide on primidone metabolism in patients with epilepsy.

Little is known about the influence of phenytoin and ethosuximide on primidone. Therefore we studied three groups of patients: 28 receiving primidone alone, 16 on comedication of primidone with phenytoin and 9 on primidone plus ethosuximide. Antiepileptic drug determinations were done with Kupferberg's gas chromatographic method. The results show that the addition of phenytoin--but not ethosuximide--does increase the plasma concentration of phenobarbital derived from primidone but not of primidone itself. The phenobarbital/primidone plasma concentration ratio is with 4.2 +/- 0.7 (+/- S.E.) significantly (P less than 0.001) higher in patients receiving primidone and phenytoin as compared to those on primidone alone (1.6 +/- 0.2) or together with ethosuximide (1.4 +/- 0.7). The effect of phenytoin occurs and persists for several days after the steady state plasma concentration of phenytoin has been reached. This effect is probably not due to induction of enzymes hydroxylating primidone but rather to inhibition of the metabolism and/or excretion of phenobarbital. A case of phenobarbital intoxication due to addition of phenytoin to primidone medication is described in detail.

Drug Interactions↗

PubMed1979

Effects of valproate and ethosuximide on thalamocortical excitability.

Sodium valproate and ethosuximide are anticonvulsants employed in the treatment of petit mal epilepsy; both drugs are considered to be thalamically active. Valproate and ethosuximide both decreased the average evoked response following the second of two stimuli delivered to the ventrolateral thalamus at stimulus frequencies in the region of 3 Hz. Ethosuximide, but not valproate, enhanced the average evoked response at high stimulus frequencies an action shared with several convulsant treatments having different modes of action. The clinical effects of valproate and ethosuximide can be related to this differential modulation of thalamocortical excitability.

Animals↗

PubMedDate not supplied

Factors influencing plasma concentrations of ethosuximide.

The relation between steady-state plasma ethosuximide level and drug dose was studied in 46 patients. In this population, plasma drug levels were proportional to drug dose, expressed on a body weight basis. Age did not alter this relationship, but plasma levels increased more rapidly, relative to dose, in females than in males. Intake of methylphenobarbitone, but not intake of certain other anticonvulsants (phenytoin, phenobarbitone, primidone and carbamazepine) altered the relationship between plasma ethosuximide level and ethosuximide dose. In individual patients, successive dose increments of equal size produced progressively greater increases in steady-state plasma ethosuximide levels. This phenomenon has obvious therapeutic implications.

Adolescent↗

PubMed1976

Effects of ethosuximide upon psychomotor responses and electromyographic parameters of healthy individuals.

The purpose of this paper was to investigate the effects of anticonvulsant ethosuximide upon physiological parameters, psychomotor reactions and electromyographic criteria. Ethosuximide increased the reaction times to flashes and the choice reaction time in most subjects, often provoked a greater amount of errors during choice reactions and decreased the average heart frequency. The functional activation during the tasks was diminished. The EEG showed no marked qualitative or quantitative changes. Ethosuximide reduced the maximum conduction velocity of the motor nerve and changed the action potential duration but not the action potential shape. There is no exact parallelism between the increase in reaction time and decrease of nerve conduction velocity. The drug effect upon psychomotor reactions seems to be caused by reduction of vigilance and an inhibitory effect upon the individual's motor responsiveness. Like other anticonvulsants, ethosuximide may alter the electrical properties of all excitable membranes and, by this ubiquitous site of action, exerts the described effects.

Action Potentials↗

PubMed1977

Comparison of enzyme immunoassay and gas chromatography for determination of carbamazepine and ethosuximide in human serum.

Patients' sera were analyzed for carbamazepine and ethosuximide by enzyme immunoassay (x) and gas chromatography (y), and the results were compared. The correlation coefficients were: for carbamazepine, x vs. y 0.94 (n = 93); for ethosuximide, x vs. y 0.99 (n = 30). These results suggest that the two methods could be used interchangeably. Ten serum samples supplemented with carbamazepine (2.5 to 12.5 mg/liter) and ethosuximide (20.0 to 130.0 mg/liter) were analyzed by both methods. The correlation coefficients were: x vs. y 0.99 (n = 10) for carbamazepine and x vs. y 0.99 (n =10) for ethosuximide.

Carbamazepine↗

PubMed1978

Exacerbation generalized nonconvulsive seizures with ethosuximide therapy.

We describe a patient whose absence seizures increased greatly in number after the addition of ethosuximide to ongoing phenobarbital therapy. This unusual response and review of other cases in the literature suggested the possibility of some as yet underfined interaction between ethosuximide and other anticonvulsant drugs. That a particular subytpe of epilepsy may be worsened by ethosuximide therapy is also considered.

Child↗

PubMed1977

Ethosuximide and bicuculline inhibition in petit mal epilepsy.

The mechanisms of petit mal epilepsy remain a mystery despite successful therapy. Previous workers have proposed that paroxysmal activity of cortical inhibitory systems plays a role in absence seizures. In this study, we have compared the effects of bicuculline, a potent convulsive agent and GABA antagonist, with ethosuximide, a drug used to treat petit mal epilepsy, on the thalamocortical motor system of the cat. Under chloralose anesthesia, sequential pairs of pulses were delivered to ventrolateral thalamus (VL) varying either pulse amplitude or interval. The evoked responses were recorded from sensorimotor cortex, analyzed on-line by computer, and plotted as an excitability curve (mean response amplitude as a function of pulse interval), or a family of threshold curves (mean response amplitude as a function of stimulus amplitude at various fixed intervals). Administration of each drug resulted in increased thalamocortical excitability and decreased threshold to stimulation for short pulse-pair intervals, with diminished duration of the excitability curve. Increased alertness was produced by both drugs. Studies with grand mal anticonvulsants demonstrated entirely different effects. Because GABA is thought to be the primary inhibitory transmitter in VL and cerebral cortex, bicuculline would be expected to result in disinhibition. The similarity of the data for ethosuximide suggests that ethosuximide also suppresses inhibition in the thalamocortical motor system and adds further to the accumulating evidence of the role of inhibitory system in petit mal epilepsy.

Animals↗

PubMed1978

Urinary metabolites of 2-ethyl-2-methylsuccinimide (ethosuximide) studied by combined gas chromatography mass spectrometry.

Metabolites of 2-ethyl-2-methylsuccinimide (ethosuximide) have been studied by combined gas chromatography mass spectrometry in a urine sample from a patient treated for petit mal epilepsy with ethosuximide. A new metabolite, 2-carboxymethyl-2-methylsuccinimide, was identified in the urine. It is presumably formed by omega 1-hydroxylation of the ethyl sidechain of the drug followed by a further oxidation of the primary alcohol to a carboxyl group. A previously identified metabolite, 2-ethyl-3-hydroxy-2-methylsuccinimide, was shown in the present study to yield two gas chromatographic peaks (as the N-methylated compound), indicating the existence of a diastereoisomeric pair. Thus, the enzyme responsible for the ring hydroxylation is probably not stereospecific, or alternatively two enzymes with different stereospecificity may exist.

Adolescent↗

PubMed1977

Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway.

The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug.

Animals↗

PubMed1977

Time-dependent kinetics II: Diurnal oscillations in steady-state plasma ethosuximide levels in rhesus monkeys.

Morning steady-state (9 am) plasma levels were significantly higher than the corresponding evening (5 pm) plasma levels during a 3-week zero-order infusion of ethosuximide to six monkeys. These differences could not be explained by experimental variables such as GLC assay and infusion pump. Circadian periodicity in steady-state plasma levels was investigated in three monkeys over 4 months under controlled experimental conditions: blood sampling at 2-hr intervals for 26 hr, 1 day/week; fixed lighting, feeding, and noise schedules; and electroencephalogram monitoring. The plasma concentration-time curves showed two minima in the 12 noon-2 pm and 8 pm-12 midnight periods, and the later involved the largest percent change in plasma levels (4-8%). The plasma concentration-time data were subjected to cross-correlation analysis, which indicated a circadian rhythm in steady-state plasma levels with a period of 24-26 hr.

Animals↗

PubMed1978

Consecutive gas chromatographic determination of phenytoin, phenobarbital, primidone, phenylethylmalondiamide, carbamazepine, trimethadione, dimethadione, ethosuximide, and valproate from the same serum specimen.

A quantitative gas-liquid chromatographic procedure is described for the consecutive determination of phenytoin, phenobarbital, primidone, phenylethylmalondiamide, carbamazepine, trimethadione, dimethadione, ethosuximide and valproate from a single serum specimen of 1.2 ml. After extraction from serum by two different procedures, the anticonvulsants are chromatographed without further purification on a 3% OV 17 column either with or without derivative formation by means of "on-column" methylation. Multiple internal standards are employed in order to enhance the reproducibility of drug-concentration measurement.

Anticonvulsants↗

PubMed1977

Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum by high-pressure liquid chromatography.

We present a method for simultaneously determining five anticonvulsants [phenobarbital, phenytoin (diphenylhydantoin), primidone, ethosuximide, and carbamazepine] in as little as 25 microliters of serum. The proteins are precipitated with an acetonitrile solution containing hexobarbital as an internal standard. The anticonvulsants are eluted from a reversed-phase column with a mobile phase consisting of an acetonitrile/phosphate buffer (19/81 by vol) at a flow rate of 3.0 ml/min. The eluted drugs are detected by their absorption at 195 nm, and quantities estimated from their peak heights. Each analysis requires about 14 min. at an optimum column temperature of 50 degrees C. The lower unit of detection for all of these drugs is less than 10 ng. Sensitivities, for serum samples, of 1.0 mg/liter for all the drugs analyzed are attained routinely. Analytical recoveries for the five drugs varied from 97 - 107%, with good day-to-day precision (CV between 3.9 and 5.9%). Of more than 30 drugs tested for possible interference, only ethotoin interferes with the analysis of phenobarbital.

Anticonvulsants↗

PubMed1975