SEARCH · PubMed Health

Results for “Primidone”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1977

Intoxication with primidone: continuous monitoring of serum primidone and its metabolites during forced diuresis.

An 18 year old girl is reported, who ingested 15 g of primidone (Liskantin), 330 mg/kg, to commit suicide. Continuous monitoring of the serum levels of primidone, PEMA, and phenobarbital revealed increased elimination of primidone by forced diuresis (6000 ml/24 hours). It is concluded that forced diuresis inhibits the otherwise mandatory increase in primidone metabolites, PEMA and phenobarbital. It is suggested that even after improvement of the clinical symptoms forced diuresis should be continued for at least 48 hours. In epileptic patients the reinstitution of primidone therapy should be considered only on the third day after accidental ingestion, if the clinical symptoms have improved, and if there is no possibility of immediate determination of primidone serum levels.

Adolescent↗

PubMed1978

[Ratio of primidone to phenobarbital serum levels as a criterion in the assessment of anticonvulsive therapy with primidone (author's transl)].

Serum levels of primidone and phenobarbital were measured and showed a relatively constant ratio in patients under primidone monotherapy. In outpatients, however, this ratio was lower and the range of its values wider than in hospitalized children, and the difference was significant (1:2.05 or 1:2.95). The reason for this turned out to be irregular intake of the drug by the outpatients. The ratio of primidone to phenobarbital serum levels offers itself as a control of regularity of intake of primidone.

Adolescent↗

PubMed1977

Effect of primidone concentration on glass transition temperature and dissolution of solid dispersion systems containing primidone and citric acid.

The glass transition temperatures of glasses containing various concentrations of primidone in citric acid were measured and found to increase as the primidone concentration increased. Dissolution studies of these systems and particle-size measurements of primidone precipitated during dissolution of devitrified glasses suggest that the increase in the dissolution rate of the devitrified systems is due to both the small size of the precipitated crystals and the excellent wettability of these systems.

Chemistry, Pharmaceutical↗

PubMed1992

Single-dose kinetics of primidone in human subjects: effect of phenytoin on formation and elimination of active metabolites of primidone, phenobarbital and phenylethylmalonamide.

Effect of repetitive administration of phenytoin (PHT) on the single-dose pharmacokinetics of primidone (PRM) was investigated in 3 healthy male subjects. The peak concentration of unchanged PRM was achieved at 12 and 8 h after the administration of PRM in the absence and the presence of PHT, respectively. The elimination half-life of PRM was decreased from 19.4 +/- 2.2 (mean +/- S.E.) to 10.2 +/- 5.1 h (p < 0.05) and the total body clearance was increased from 24.6 +/- 3.1 to 45.1 +/- 5.1 ml/h/kg (p < 0.01) in the presence of PHT. No significant change was observed for the apparent volume of distribution between the two treatments. In the absence of PHT, the measurable amount (> or = 0.1 mumol/l) of phenobarbital (PB) and phenylethylmalonamide (PEMA) did not appear in the serum until 5.3 and 1.3 h after the PRM administration, and the peak concentrations of PB and PEMA were achieved at 52 and 36 h, but the concentrations of both metabolites were very low (PB 1.3 mumol/l; PEMA 1.7 mumol/l). In the presence of PHT, within 0.8 and 0.5 h after the administration of PRM, the derived PB and PEMA appeared in the serum. About a 6-fold increase in the peak concentrations of both the metabolites were observed (PB 8.2 mumol/l; PEMA 11.0 mumol/l). No significant changes were observed for the elimination half-lives of both PB and PEMA in the absence and presence of PHT.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗

PubMed1975

Acute primidone overdosage with massive crystalluria.

A patient admitted to the hospital in coma was found to have massive primidone crystalluria. Gas chromatographic analysis of blood and urine for primidone and phenobarbital showed high urine primidone levels and high blood phenobarbital levels. The primidone levels suggest that primidone is rapidly cleared into urine. The high blood phenobarbital levels within 12 hr of overdosage with a history of diphenylhydantoin therapy and without phenobarbital therapy or overdosage suggests that diphenylhydantoin may influence the metabolic conversion of primidone to phenobarbital. The relationship of clinical symptomatology to high levels of primidone and phenobarbital is unclear. Analysis of blood and urine for primidone and phenobarbital and urine for crystals is of value in establishing diagnosis and prognosis in cases of suspected primidone overdosage.

Child↗

PubMed1977

[The effect of primidone treatment of thyroid hormones in epileptic children and adolescents (author's transl)].

In primidon-treated patients there are significantly decreased serum concentrations of total and free thyroxin, protein bound iodine and base line serum TSH values. In primidon-treated children T3-resin test values, concentration of thyroxin-binding protein and total cholesterol are identical to those of the control group. Degree of diminution in serum concentration of protein bound iodine, total and free thyroxin and base line TSH was independant of the primidon dose per day. Probably the demonstrated alteration in the thyroid function tests studied, is mainly caused by phenobarbital, the major metabolite of primidon and not directly by unmetabolized primidon. It is suggested that the high protein-binding capacity of phenobarbital results in a competitive displacement of protein bound thyroxin comparable to that of DPH. Phenobarbital is know to be a stimulator of the drug metabolizing enzyme system in the liver. This effect may be the cause of an increased turnover of T4 which results in a decreased serum concentration of total and free T4 at last. It seems possible that there is a balance in serum concentration of thyroid hormones on a lower level. Normal euthyroid state may be presumed, if T4-secretion raises, but there is no clue for an increased pituarity response. In contrast to the normal group in primidon-treated children the base line serum TSH values are decreased. It is supposed that another effect of primidon is responsible for this fact. There may be an influence of primidon treatment on hypothalamic pituarity axis. Our findings do not indicate clearly a hypothyroid state in primidon-treated patients; further investigations should give an answer to the guestion, if side effects as tiredness, decreased impetus and constipation are not partly caused by alterations in thyroid hormone system.

Adolescent↗

PubMed1979

Pharmacokinetics of primidone and its active metabolites in the dog.

In dogs, the metabolism of primidone and the pharmacokinetics of the drug itself as well as its metabolites phenobarbital and phenylethylmalonic acid diamide (PEMA) was followed after single oral doses of 30 mg/kg (0.14 mmole/kg). Primidone was rapidly absorbed, so that maximal serum concentrations were reached after 2 hr, the concentration fell then with a half-life averaging 5 hr in Beagles and 10 hr in Mongrels. PEMA appeared in plasma with a ka of 0.003--0.005 min-1, reached maximal concentrations after about 6.5 hr in Beagles and 12 hr in Mongrels. The elimination half-life averaged 7.5 hr in Beagles and 14 hr in Mongrels. After single oral doses, phenobarbital could only be detected in low concentrations in some Beagles. Phenobarbital had an elimination half-life of 32 +/- 4.8 hr in Beagles and of 70 +/- 16 hr in Mongrels. During continued treatment with daily doses of 30--50 mg/kg primidone, steady-state concentrations of about 15 micrograms/ml (65 nmole/ml) were reached after 6--8 days, the PEMA concentrations showed rather pronounced fluctuations around average values of 8--10 micrograms/ml (39--49 nmole/ml), whereas the concentrations of primidone mainly remained below 5 micrograms/ml (23 nmole/ml). In mice, the anticonvulsant potency of the 3 drugs was determined: Elevations of the electroconvulsant threshold by 40 V were produced by 0.01 mmole/kg of phenobarbital, 0.017 mmole/kg of primidone or 0.37 mmole/kg of PEMA. Taking the anticonvulsant potency of the 3 drugs into consideration, phenobarbital is responsible for more than 85% of the total anticonvulsant activity during continued medication of primidone. The penetration of primidone and its metabolites into the cerebro-spinal fluid was followed: phenobarbital reached steady state levels already after 1--1.5 hr, primidone and PEMA not before 2.5 hr. The concentrations in CSF roughly corresponded to the free drug in plasma. On account of the similarities in metabolism and pharmacokinetics of primidone in dog and man, the former species seems to be a suitable model in epilepsy research. Differences between both species are most pronounced in the Beagle.

Animals↗

PubMed1976

A comparison of the effectiveness of primidone versus carbamazepine in epileptic outpatients.

Prior to the release of carbamazepine for the treatment of patients with psychomotor and grand mal seizures, primidone was regarded as the drug of choice for these disorders, especially when combined with diphenylhydantoin (DPH). It was, therefore, of interest to compare the effectiveness of carbamazepine against primidone when added to a therapeutic dose of DPH. Forty-five patients completed a 6-month study with each patient serving as his own control. The patients were initially stabilized on therapeutic doses of DPH and one of the test compounds, while all other medications were withdrawn. After 3 months of treatment, they were transferred onto the other drug for a second 3-month period. Extensive laboratory testing, including anticonvulsant levels, electroencephalograms, and neuropsychological evaluations, was performed. For the most part, the patients remained on outpatient status, returning for reports of seizure frequency, side effects, and laboratory studies every 14 days. The study was conducted in a single blind fashion by the treating neurologists; double blind by the electroencephalographer and psychologists. The results indicated that the two drugs did not differ in their effectiveness on seizure control. There were somewhat more side effects--none serious--with carbamazepine than with primidone. The EEG showed increased fast activity with primidone and increased theta activity with carbamazepine. There was no difference in regard to decrease of electroencephalographic seizure discharges. The patients showed more impairment on a repeatable neuropsychological test battery with primidone than with carbamazepine, and they also showed an increase on the psychopathic deviate scale of the Minnesota Multiphasic Inventory. Depressive feelings, when present, lessened while under treatment with carbamazepine. The results suggest that patients with the seizure types under consideration and who do not respond to DPH alone or to a DPH-phenobarbital combination can be placed on either carbamazepine or primidone while phenobarbital is discontinued. A patient who is intellectually and emotionally intact with no past history of behavioral disturbances may do better on primidone than carbamazepine, because this drug gives fewer side effects. On the other hand, those patients who have a past history of emotional and/or intellectual disturbances may profit more from carbamazepine.

Adolescent↗

PubMed1979

Flow-dependent salivary primidone levels in epileptic children.

In 36 epileptic children treated with primidone alone or in combination with additional anticonvulsants, salivary drug levels were compared in resting (I) and in flow-stimulated (II) saliva and were related to the corresponding serum levels. Primidone levels in saliva I and saliva II were highly correlated (r = 0.97) but were significantly (p less than 0.001) lower in saliva II; the mean difference was -38%. Serum primidone levels were highly correlated to salivary primidone levels both in saliva I (r = 0.92) and in salvia II (r = 0.91). A significant negative correlation could be established between the salivary flow rate and the saliva/serum ratio of primidone, especially in saliva I (r = 0.61; p less than 0.001). The mean saliva I/serum ratio was 1.115, reflecting drug accumulation in resting saliva. The reason primidone accumulates remains unclear. When salivary flow was stimulated, the mean saliva/serum ratio decreased to 0.7, indicating the development of a drug concentration slope from blood to saliva. This is explained by the limited permeation of the drug through cellular membranes due to its rather low lipid solubility. From the data it can be concluded that saliva is suitable for monitoring primidone levels provided the conditions of sample collection are standardized.

Anticonvulsants↗

PubMed1978

Epileptiform seizures in domestic fowl. VIII. Anticonvulsant activity of primidone and its metabolites, phenobarbital and phenylethylmalonamide.

Primidone is an effective anticonvulsant against seizures induced in epileptic fowl by exposure to intermittent photic stimulation. Epileptic fowl metabolize primidone to phenobarbital. Pretreatment of epileptic fowl with SKF 525A to prevent the metabolism of primidone to phenobarbital indicated that primidone itself had anticonvulsant activity. Phenylethylmalonamide, a second metabolite of primidone, did not have anticonvulsant activity when administered at the same dose as primidone.

Animals↗

PubMed1975

Interaction of phenytoin and primidone.

The ratio of derived phenobarbitone to unmetabolized primidone in the serum was significantly higher in 50 epileptic patients on a combination of primidone and phenytoin than in 12 patients on primidone alone, though the dose and serum levels of primidone were similar in the two groups. Out of 253 patients attending a seizure clinic 47% were taking a combination of these two anticonvulsants. The effect of phenytoin on the metabolism of primidone may have clinical implications in view of the frequency of their combined use.

Adolescent↗

PubMed1977

Plasma level studies of primidone and its metabolites in the mouse at various stages of pregnancy.

1. Mice were treated with a teratogenic dose of primidone (100 mg/kg) by gastric intubation at three different times during pregnancy, viz. days 6-14, days 12-14 on day 14 only. Blood samples were taken on day 14 at 1, 4, 8 and 24 h after dosage. Primidone and its metabolites phenylethylmalondiamide (PEMA), and phenobarbitone, were assayed by g.l.c. 2. There was no accumulation of the parent compound or the metabolites after repeated administration of primidone; each of the substances was cleared from the plasma within 24 h. 3. The rate of metabolism of primidone increased with prolonged treatment. The peak concentration of the metabolites was higher in the two multiple-dose groups than in the single dose group. 4. The concentration of PEMA exceeded that of primidone between 3-8 h and then began to decrease in the multiple-dose groups, a similar pattern was established for phenobarbitone also, although the concentrations were lower than those of PEMA.

Animals↗

PubMed1975

[Investigations of serum levels of drugs in children receiving anticonvulsant medication. I. General evaluation of serum concentrations of diphenylhydantoin, primidone and phenobarbitone (author's transl)].

With the aid of our own method of gas chromatography we determined serum concentrations of anticonvulsants in a large number of children who were being treated with diphenylhydantoin, primidone and phenobarbitone. The drugs were being prescribed either as monotherapy, or in combination with each other, or with other substances which have anticonvulsive activity. Regression lines showed good correlations between the quantity of drugs administered (total daily dose) and serum concentrations. The regression lines for diphenylhydantoin and primidone, however, showed no differences, irrespective of whether they were being given alone or in combination. In view of the frequency of symptoms of intoxication and of non-responders, we established a therapeutic range for diphenylhydantoin and primidone (diphenylhydantoin: 5--16 mcg/ml; primidone: 4--14 mcg/ml). The required serum concentrations could be obtained by giving 8--12 mg/kg of diphenylhydantoin, and 15-22 mg/kg of primidone. In spite of the satisfactory correlation between total daily dose and serum concentrations, however, many patients showed departures from this normal behaviour, especially where combination treatments were being conducted. This demonstrates the necessity for routine controls of serum levels.

Adolescent↗

PubMed1979

[The influence of primidone on thyroid function (author's transl)].

The influence of primidone on thyroxine level, T3 index, FT4 index, triiodothyronine level, T3 (RIA)/T4 (RIA) quotient as well as on the TSH basal and stimulated values was investigated in 30 children on long-term treatment. The values obtained were compared statistically with those of a normal group. During primidone treatment a drop in T4 level and in FT4 index as well as an increase in T3 (RIA)/T4 (RIA) quotient was observed. On the other hand the triiodothyronine level and the T3 index were not influenced. The TSH basal and stimulated values were not statistically different from the control group. Thus the primidone-treated children are euthyroid according to the TRH test. Primidone probably stimulates hepatocellular thyroxine breakdown.

Child↗

PubMed1975

Diphenylhydantoin, phenobarbital, and primidone in saliva, plasma, and cerebrospinal fluid.

Diphenylhydantoin, primidone, and phenobarbital were determined in saliva and plasma of 164 patients by gas-liquid chromatography. The saliva ratio was about one-tenth in patients on diphenylhydantoin, 0.32-0.38 on phenobarbital alone and with other drugs, 0.97 and 0.96 on primidone alone and with other drugs. The S/P ratio of phenobarbital was similar in patients treated with primidone alone or with co-medication. For diphenylhydantoin and primidone, the S/P and CSF/plasma ratio were similar; for phenobarbital the S/P ratio was lower due to the difference in pH of saliva and CSF. Thus the concentration in saliva serves as a measure of the nonprotein-bound or free concentration in plasma with the advantage that saliva is easy to obtain. Co-medication does not change the S/P ratio for the three drugs studied. The high correlation between levels in plasma and in saliva allows the plasma levels to be predicted from the concentration in saliva.

Humans↗

PubMed1975

Isoniazid as an inhibitor of primidone metabolism.

Isoniazid inhibited the metabolism of primidone in a patient with focal seizures. The steady-state serum level of primidone rose when the patient received both drugs simultaneoulsy. The serum levels of the primidone metabolites, phenobarbital and phenylethylmalonamide, fell and the rate of metabolism of primidone decreased. The results are similar to those observed when isoniazid is adminstered with diphenylhydantoin.

Depression, Chemical↗

PubMed1975

Therapeutic monitoring of anticonvulsant drugs: gas-chromatographic simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin.

We describe a sensitive and precise gas-chromatographic method in which benzylmalonate methylester monoamide is used as the internal standard for the simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin. The trimethylsilyl derivatives of the anticonvulsants are well separated from each other and from normal serum constituents. The lower limit of detection for each drug is 0.5 mg/liter when 1 ml of serum is analyzed. Within-run precision (CV), established by analysis of 10 replicates, was as follows: primidone (5.4 mg/liter), 2.6%; phenylethylmalonamide (5.5 mg/liter), diphenylhydantoin (6.6 mg/liter), 3.8%; and carbamazepine (10.4 mg/liter), 3.2%. Fifty specimens were analyzed for primidone and 35 for diphenylhydantoin by a standard gas-chromatographic method involving on-column methylation and by the procedure we have developed. The mean value observed for primidone with the on-column alkylation procedure was 9.3 mg/liter and with our procedure was 9.6 mg/liter. When values for our assay were regressed against values for the standard method, the slope of the least-squares line was 0.936, the intercept was 1.00 mg/liter, and r was 0.939. The mean values observed for diphenylhydantoin by on-column methylation and with our procedure were both 12.6 mg/liter. When values for our assay were regressed against the standard method, the slope of the least-squares line was 0.944, the intercept was 0.3 mg/liter, and r was 0.988.

Anticonvulsants↗