Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Primidone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 73 records · Page 4Linked to original sources
PubMed1990

The disposition of primidone in elderly patients.

1. The pharmacokinetics and metabolism of primidone at steady-state were studied in 10 elderly patients aged 70-81 years and eight control subjects aged 18-26 years. 2. Primidone half-lives and clearance values (mean +/- s.d.) were similar in the elderly and in the young (12.1 +/- 4.6 vs 14.7 +/- 3.5 h and 34.8 +/- 9.0 vs 33.2 +/- 7.2 ml h-1 kg-1 respectively. 3. The serum concentrations of the metabolites phenylethylmalonamide (PEMA) and phenobarbitone relative to those of parent drug were higher in the elderly than in the young, the difference being significant (P less than 0.01) in the case of PEMA. 4. The renal clearances of primidone, phenobarbitone and PEMA were moderately decreased in the elderly but this reduction was statistically significant only for PEMA. Elderly patients excreted a reduced proportion of unchanged primidone and an increased proportion of PEMA in urine. 5. Ageing is associated with a greater accumulation of PEMA, which is unlikely to have a major clinical significance.

Adolescent↗
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↗
PubMed1981

The effects of phenytoin on phenobarbitone and primidone metabolism.

Serum concentrations of primidone and its metabolites-phenobarbitone and phenylethylmalonamide-were measured in 40 epileptic patients receiving treatment with primidone alone or primidone plus phenytoin. Serum phenobarbitone concentrations were also measured in 100 patients receiving phenobarbitone, alone or with phenytoin showed raised serum phenobarbitone concentrations. Phenytoin also caused raised phenylethylmalonamide concentrations in patients on primidone.

Adult↗
PubMed1984

Anticonvulsant effect of primidone in the gerbil. Time course and significance of the active metabolites.

The anticonvulsant effect of primidone was determined in gerbils, in which seizures were elicited by a blast of compressed air, over the time range of 30 min to 18 h after oral administration. ED50s remained fairly constant from 1 to 12 h after administration: 46-73 mumol/kg with the minimal value at 6 h. Of the metabolites, phenobarbital was maximally effective at 2 h after administration (ED50 35 mumol/kg), whereas phenylethylmalondiamide (PEMA) only had a weak anticonvulsant effect (ED50 1.55 mmol/kg at 2 h). By determination of primidone and its active metabolites in plasma and brain at 1, 4 and 12 h after administration of the respective ED50s, it could be shown that unchanged primidone is mostly responsible for the anticonvulsant effect of the first hours, but, at 12 h, only phenobarbital could be detected in both tissues. PEMA could not be detected in brain. From the effective brain concentrations at different times it could be calculated that primidone and phenobarbital have the same anticonvulsant potency on a molar base in the gerbil. The concentrations necessary to control seizures in this model were considerably lower than those needed to suppress convulsions in maximal seizure models in mice and rats.

Administration, Oral↗
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↗
PubMedDate not supplied

Poor correlation between single-dose data and steady-state kinetics for phenobarbitone, primidone, carbamazepine and sodium valproate in children during monotherapy. Possible reasons for the lack of correlation.

An investigation was performed to determine the relationship between the serum drug concentration/dose ratio at 24 hours following a first dose and that at steady-state for phenobarbitone, primidone (as phenobarbitone and as primidone), carbamazepine and sodium valproate, in order to assess the utility of this method in clinical practice. The drugs were given as monotherapy to 63 children for the treatment of epilepsy or febrile convulsions. The correlation between concentration/dose ratios, instead of between serum concentrations, was investigated with the aim of allowing the use of variable doses. The correlation coefficients were: r = 0.30 for phenobarbitone; r = 0.05 for phenobarbitone derived from primidone; r = 0.38 for primidone; r = 0.19 for carbamazepine; and r = 0.52 for sodium valproate. None of these correlation coefficients differed statistically from 0. These low correlation coefficients contrast with the acceptable results found by other authors for other drugs, indicating that several factors may have a greater influence on this correlation than earlier investigations suggest. The poor correlation obtained emphasises the need for clinical verification of mathematical models based on theoretical considerations which do not always apply in practice.

Age Factors↗
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↗
PubMed2003

[Antiepileptic primidone shortly to be withdrawn from sale: change medication now].

The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis. Most primidone users are elderly patients who have been prescribed this drug for many years. Changing to a new drug constitutes a health risk for them. If primidone treatment is discontinued too quickly, withdrawal seizures may appear, some of which may be severe. In patients who have not suffered an epileptic seizure for many years, discontinuing medication may be considered. Whenever continuation of anticonvulsive treatment is desirable, it may probably be a good idea to switch over to some newer antiepileptic drug. If a simple and quick substitution is essential, primidone may be replaced by its main metabolite: phenobarbital. General practitioners and neurologists are strongly advised to alter patients' medication in good time.

Anticonvulsants↗
PubMed1984

Serum concentrations and efficacy of phenytoin, phenobarbital, and primidone in canine epilepsy.

Serum concentrations, drug dosages, and seizure control were monitored in 142 dogs on a variety of anticonvulsant treatment regimens, using phenytoin, primidone, and phenobarbital. In 1 of 77 dogs receiving phenytoin, seizures were controlled with a serum concentration of 2.3 micrograms/ml. In 20 of 42 dogs receiving phenobarbital, seizures were controlled with serum concentrations ranging from 14.3 to 43.1 micrograms/ml. In 12 of 23 dogs given primidone, seizures were controlled with similar concentrations of phenobarbital derived from the primidone. Of the dogs in which seizures were uncontrolled by either of these 2 agents, a large proportion had serum phenobarbital concentrations that appeared to be inadequate in spite of what was considered adequate dosage. Further, for dogs given phenobarbital, there was a sixfold variation between dosage and achieved serum concentration, whereas dogs given primidone manifested even greater variability between dosage and serum concentration. This underscores the need for serum concentration monitoring as an adjunct to any drug protocol in seizure control since effectiveness is correlated far better with serum concentrations than with oral dosage. On the basis of these findings, a rational approach to the pharmacologic control of seizures in epileptic dogs was devised.

Animals↗
PubMed1982

Treatment of canine epilepsy with primidone.

Forty-seven dogs with a history of generalized recurrent seizures were treated with primidone at a daily oral dosage of 13 to 100 mg/kg of body weight, divided into 2 to 3 doses. During treatment, plasma concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide, were determined at irregular intervals. Of the 30 dogs that finally could be evaluated, 20 were brought to excellent or good control of their seizures by daily primidone dosages ranging from 13 to 17 mg/kg and at plasma phenobarbital concentrations of 6 to 37 micrograms/ml. Of the other 10 dogs, 5 improved to a minor extent and 5 did not improve at all. It was concluded that treatment of seizures should start with a daily dosage of 10 to 15 mg/kg, with the dosage being increased to about 35 mg/kg within a few weeks. For dogs in which the seizures are not controlled by this dosage, a further increase should be tried until a plasma phenobarbital concentration of 30 to 40 micrograms/ml is reached or until signs of drug toxicosis develop. Monitoring of plasma phenobarbital concentrations is sufficient for the control of treatment with primidone.

Administration, Oral↗
PubMed1977

Acetazolamide-induced interference with primidone absorption. Case reports and metabolic studies.

Effects of acetazolamide on primidone plasma levels were studied in three patients. Apparent interaction occurred in two patients. Primidone was not detected in the plasma when given orally with acetazolamide in one patient. In another, peak serum concentration was delayed, with corresponding delays in urinary excretion of primidone and metabolites. Plasma and urine concentrations of the two metabolites, phenylethylmalonamide and phenobarbital, were also studied.

Acetazolamide↗
PubMed1984

Spastic dysphonia and essential (voice) tremor treated with primidone.

Primidone has been reported to be effective in reducing tremor in patients with benign essential tremor. There is at least one report that suggests that the medication may reduce voice tremor, a frequent component of the essential tremor syndrome. Three patients with spastic dysphonia of essential (voice) tremor and one with more typical essential (voice) tremor were treated with primidone and experienced no alleviation in the voice signs. The side effects experienced by all patients were consistent with those noted in previous reports. Primidone does not seem to be effective in treating essential voice tremor or spastic dysphonia of essential voice tremor.

Aged↗
PubMed2002

Randomized trial comparing primidone initiation schedules for treating essential tremor.

Early side effects are common when primidone is used to treat essential tremor, with as many as one-third of patients failing to tolerate the tablets. Lower doses can be prescribed initially using a suspension formulation. We suspected suspension initiation would result in fewer early side effects, allow better acclimatization, and improve compliance. Forty patients with essential tremor were randomized to begin primidone treatment using either 2.5 mg doses in the suspension form or 25 mg doses in the tablet form. Doses gradually increased over 3 weeks to 150 mg/day. This was a double-blind, double-dummy trial. Medication cessation due to side effects was designated the primary end-point. Four patients in the suspension group and two in the tablet group dropped out due to early side effects, resulting in a relative risk of 1.9 (95% confidence interval 0.4 to 9.2). Side effects in the first 48 hours of treatment were equally common, affecting seven subjects in each group. Treatment benefits were the same in both groups. We concluded that use of a very low initial dose and a graduated titration schedule in suspension formulation did not appear to improve primidone tolerability. If anything, compliance tended to be worse when compared with the tablet formulation, though the study was under-powered to reject the null hypothesis of equivalence.

Administration, Oral↗
PubMed1987

Effect of chronic primidone treatment on folate-dependent one-carbon metabolism in the rat.

Rats were treated chronically with primidone (100 mg/kg/12 hr, p.o.) for up to 8 weeks. The effects of this treatment on one-carbon metabolism were determined in brain and liver. Serine hydroxymethyltransferase activity increased in both brain (44%) and liver (50%). Methylenetetrahydrofolate reductase activity increased in liver (26%) with a significant correlation to the length of treatment, but in brain it was unchanged. Methyltetrahydrofolate:homocysteine methyltransferase activity increased in brain (43%) with a significant correlation to length of treatment, but in liver no effect was observed. Methionine adenosyltransferase activity in brain was significantly lower than control at only one point after 8 weeks of chronic treatment. S-Adenosylmethionine concentration in liver increased gradually (23%) during treatment. S-Adenosylhomocysteine concentrations decreased in brain (33%) and increased in liver (23%) with chronic primidone treatment. These data support the hypothesis that chronic primidone treatment leads to folate depletion through interference with folate metabolism.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2005

Primidone is associated with interictal depression in patients with epilepsy.

Depressive symptoms are common in epilepsy. To determine associations between depression and demographic, clinical, and pharmacological factors among epileptic patients, we conducted a cross-sectional survey. We evaluated 241 epileptic outpatients at a neurological center in a 6-month period. Depressive syndrome was diagnosed when both the Montgomery-Asberg Scale and the Beck Depression Inventory were rated above the standard cutoff points. Bivariate and multivariate analyses were performed to assess the differences between depressed and nondepressed patients with respect to demographic, clinical, and pharmacological features. Depressive syndrome was diagnosed in 42.7% of patients (n=103). Factors associated in the bivariate analysis were: cryptogenic etiology, posttraumatic epilepsy, use of primidone, and inadequate seizure control. After logistic regression, inadequate seizure control (OR 3.08, 95% CI 1.40-6.77, P=0.005) and use of primidone (OR 4.08, 95% CI 2.09-7.98; P<0.001) remained significantly associated. Depression was common and associated with inadequate seizure control and use of primidone.

Adult↗
PubMed1998

Lack of in vivo/in vitro correlations for 50 mg and 250 mg primidone tablets.

PURPOSE: To determine if large differences in the in vitro dissolution profiles for primidone tablets would result in significant bioavailability differences. METHODS: Two separate bioavailability studies were conducted. The first study used 18 healthy subjects and compared the bioavailability of an old 50 mg tablet formulation, a new 50 mg tablet formulation, and a suspension containing 50 mg/ml of primidone. The second study enrolled 24 subjects who were to receive a new 250 mg tablet formulation, two lots of an old 250 mg tablet formulation and a 250 mg tablet from a second manufacturer. In vitro dissolution was conducted over 90 minutes, using USP 23 Apparatus 2 at 50 rpm, with 900 ml of water. RESULTS: Dissolution at 90 minutes for the old and new 50 mg tablets was approximately 20% and 100%, respectively. The dissolution of the four 250 mg tablets ranged from approximately 30% to 100%. The 50 mg tablet that dissolved slower had a longer Tmax and a 14% lower Cmax than the more rapidly dissolving tablet, but the AUC(0-infinity) values differed by only 3%. Only nine subjects completed the 250 mg study because of side effects. The differences in Cmax and AUC(0-infinity) among the four 250 mg tablets were less than 7%. CONCLUSIONS: Even though there were large differences in the in vitro dissolution of the 50 mg and the 250 mg primidone tablets, the two 50 mg tablets were shown to be bioequivalent, as were the four 250 mg tablets.

Adult↗
PubMed1999

The use of primidone in the treatment of refractory bipolar disorder.

Four anticonvulsant medications (carbamazepine, valproate, gabapentin and lamotrigine) have received attention in the psychiatric literature as efficacious treatment for bipolar disorder, either as monotherapy or as adjunctive agents. Although two earlier reports in 1993 suggested that primidone may also be helpful for bipolar disorder, this older anticonvulsant has not been evaluated in any subsequent studies to confirm these earlier findings. In the present prospective open study, 26 patients with refractory bipolar disorder were treated with primidone as an adjunctive therapy. Eight (31%) patients experienced a persistent positive therapeutic effect. Five (19%) patients were considered partial or temporary responders to primidone. The remaining 13 patients (50%) were considered treatment failures. Although a 31% response rate is considered modest in most psychotropic medication studies, the authors believe that this success rate is significant in this refractory patient population and should provide impetus for future more scientific studies to confirm the preliminary findings of this open trial.

Adult↗