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Environmental Monitoring and Assessment Mar 2019The current study addresses the removal of an emerging environmental contaminant (primidone) in batch adsorption experiments using commercial-grade powdered activated...
The current study addresses the removal of an emerging environmental contaminant (primidone) in batch adsorption experiments using commercial-grade powdered activated charcoal (PAC). The experiments for the removal of primidone were performed to identify the effect of various adsorption parameters. The second-order rate expression best represented the adsorption kinetics data. The Freundlich isotherm equation was best fitted to the experimental adsorption data at equilibrium for removal of primidone using PAC. The values for change in entropy (ΔS) were positive, which indicates that the degree of freedom of the process increases. The negative values of change in enthalpy (ΔH) and change in Gibb's free energy (ΔG) indicate that the physical adsorption is a dominant phenomenon, and the process is feasible and spontaneous. The negative value of ΔH also represented the exothermicity of the adsorption process. The Taguchi optimization technique calculated the influence of variation of different process parameters, viz., initial pH (pH), PAC dosage (m), initial adsorbate concentration (C), solution temperature (T), and process contact time (t), on the removal of primidone by adsorption from aqueous solution. Each of the above parameters was examined at three levels to study their effects on the adsorptive uptake of primidone using PAC (q, mg g), and the optimum value necessary to maximize q was determined. The findings from the ANOVA indicate that the PAC dose (m) is the most notable parameter contributing 62.16% to q and a 71.96% to the signal to noise (S/N) ratio data, respectively. The confirmation experiments performed at the optimum parameter condition validated the applicability of the Taguchi design of experiments. The percent removal and adsorptive uptake at the optimal condition were 86.11% and 0.258 mg g, respectively.
Topics: Adsorption; Charcoal; Hydrogen-Ion Concentration; Kinetics; Models, Theoretical; Primidone; Temperature; Thermodynamics; Water Pollutants, Chemical; Water Purification
PubMed: 30868257
DOI: 10.1007/s10661-019-7302-x -
Drug Metabolism and Disposition: the... 1979
Topics: Animals; Anticonvulsants; Kinetics; Mice; Phenobarbital; Phenylethylmalonamide; Primidone; Time Factors
PubMed: 40779
DOI: No ID Found -
The Lancet. Neurology Feb 2011Essential tremor is a common movement disorder. Tremor severity and handicap vary widely, but most patients with essential tremor do not receive a diagnosis and hence... (Review)
Review
Essential tremor is a common movement disorder. Tremor severity and handicap vary widely, but most patients with essential tremor do not receive a diagnosis and hence are never treated. Furthermore, many patients abandon treatment because of side-effects or poor efficacy. A newly developed algorithm, based on the logarithmic relation between tremor amplitude and clinical tremor ratings, can be used to compare the magnitude of effect of available treatments. Drugs with established efficacy (propranolol and primidone) produce a mean tremor reduction of about 50%. Deep brain stimulation (DBS) in the thalamic nucleus ventrointermedius or neighbouring subthalamic structures reduces tremor by about 90%. However, no controlled trials of DBS have been done, and the best target is still uncertain. Better drugs are needed, and controlled trials are required to determine the safety and efficacy of DBS in the nucleus ventrointermedius and neighbouring subthalamic structures.
Topics: Clinical Trials as Topic; Deep Brain Stimulation; Essential Tremor; Humans; Primidone; Treatment Outcome
PubMed: 21256454
DOI: 10.1016/S1474-4422(10)70322-7 -
Journal of Veterinary Pharmacology and... Jun 1985The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand... (Comparative Study)
Comparative Study
The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.
Topics: Animals; Dog Diseases; Dogs; Epilepsy; Phenobarbital; Primidone
PubMed: 4020942
DOI: 10.1111/j.1365-2885.1985.tb00934.x -
Therapie 2012Primidone is a minor first-generation antiepileptic drug, little currently prescribed for this indication, but except marketing authorization, remains a first-line...
Primidone is a minor first-generation antiepileptic drug, little currently prescribed for this indication, but except marketing authorization, remains a first-line treatment of essential tremor. Although it is metabolized in phenyl-ethyl-malondamide and phenobarbital, active metabolites that contribute also to its action, primidone is not a prodrug and is active by itself. The rate of conversion of primidone to phenobarbital is highly variable according to the subject. Generally accepted therapeutic range for primidone is between 5 and 10 mg/L (23-46 mmol/L). The therapeutic drug monitoring (TDM) of primidone must be accompanied by the determination of phenobarbital concentrations. The level of proof of the interest of the TDM primidone was estimated to be "probably useless". Phenobarbital, a very ancient anticonvulsant, is much less used today, for the benefit of other more recent compounds. It remains prescribed in neonatology and is one of the compounds used in status epilepticus. It is a molecule with a long half-life, metabolized in p-hydroxy-phenobarbital. It is a potent inducer of CYP3A4. Several side effects, especially drowsiness, are concentration-dependent. Generally accepted therapeutic range for phenobarbital is between 10 and 40 mg/L (43 - 172 mmol/L), without considering the type of crise. The level of proof of the interest of TDM of phenobarbital was evaluated as "recommended".
Topics: Anticonvulsants; Drug Monitoring; Half-Life; Primidone
PubMed: 23110839
DOI: 10.2515/therapie/2012036 -
Neurology Dec 1989We studied the acute and chronic effects of propranolol and primidone in essential tremor by administering long-acting propranolol (80 to 160 mg/d) and primidone (50 to...
We studied the acute and chronic effects of propranolol and primidone in essential tremor by administering long-acting propranolol (80 to 160 mg/d) and primidone (50 to 250 mg/d) to 50 patients. We evaluated patients at 1, 3, 6, 9, and 12 months after treatment and assessed tremor by subjective rating by patients, clinical scoring, and thermographic (accelerometer) recordings. Acute adverse reactions occurred in 8% with propranolol and 32% with primidone. Propranolol was without therapeutic effect in 30%, and 32% had no benefit from primidone. Significant chronic side effects occurred in 17% taking propranolol and in 0% with primidone. Tolerance to drug effect occurred with chronic treatment in 12.5% of patients with propranolol and 13.0% with primidone. We conclude that propranolol and primidone are effective long-term treatment for some patients with essential tremor. Acute adverse reactions with primidone and side effects with chronic use of propranolol hamper therapy.
Topics: Aged; Drug Evaluation; Female; Humans; Male; Primidone; Propranolol; Time Factors; Tremor
PubMed: 2586774
DOI: 10.1212/wnl.39.12.1587 -
Annals of Internal Medicine Jul 1980We studied a family with the long QT syndrome. The initial case was in a patient who presented with seizures, ventricular fibrillation, and syncope. After a trial of...
We studied a family with the long QT syndrome. The initial case was in a patient who presented with seizures, ventricular fibrillation, and syncope. After a trial of conventional modalities of treatment including left stellate ganglionectomy, primidone (Mysoline) therapy was initiated. This drug has been successful in suppressing ventricular arrhythmias and shortening the QT interval over a 2-year follow-up period. Two additional family members with QT prolongation have been treated with primidone. During an 8-month follow-up, electrocardiographic and Holter recordings showed shortening of the QT interval.
Topics: Adolescent; Adult; Arrhythmias, Cardiac; Death, Sudden; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Primidone; Seizures; Syndrome
PubMed: 7396315
DOI: 10.7326/0003-4819-93-1-53 -
Deutsche Medizinische Wochenschrift... Oct 1991Two men, aged 57 and 77 years old, reported increasing unsteadiness on standing upright for the past 2 and 5 years, respectively. It had become impossible for them to...
Two men, aged 57 and 77 years old, reported increasing unsteadiness on standing upright for the past 2 and 5 years, respectively. It had become impossible for them to remain standing for more than 10 seconds, as otherwise they might fall down. Walking, sitting and lying were possible without difficulty. Both patients were found to have a fine tremor in both legs on standing only. There were no other neurological signs or symptoms. Electromyography of the leg muscles demonstrated tremor activity at 14-16 Hz. Propranolol, 40 mg three times daily, in the 57-year-old patient brought no improvement. However, on taking primidone, in slowly increasing doses up to 250 and 500 mg daily, respectively, the condition lastingly improved in both patients.
Topics: Aged; Chronic Disease; Dose-Response Relationship, Drug; Electromyography; Humans; Male; Middle Aged; Neurologic Examination; Posture; Primidone; Tremor
PubMed: 1914921
DOI: 10.1055/s-2008-1063781 -
Developmental Pharmacology and... 1988A total of 35 newborns whose mothers had been treated with either primidone (PMD), phenobarbital (PB) or a combination of one of these drugs with other antiepileptic...
A total of 35 newborns whose mothers had been treated with either primidone (PMD), phenobarbital (PB) or a combination of one of these drugs with other antiepileptic drugs were included in this study. Fetal/maternal serum concentration ratios at birth, milk/serum concentration ratios and neonatal half-lives were determined for PMD, PB and phenylethylmalondiamide (PEMA). Steady-state serum levels of PMD in 2 nursed infants were 2.5 and 0.7 micrograms/ml, respectively, for PEMA values of 1.4 and 0.4 micrograms/ml. PB steady-state concentrations ranged between 2.0 and 13.0 micrograms/ml (6 infants). Maternal PB serum protein binding did not change during and after pregnancy. Neonatal free-fraction values at birth were similar to maternal values: 63.2 +/- 17.2% (n = 11). In the postnatal period, however, PB free-fraction values rose to more than 90% in some infants. In one case, neonatal free concentrations of PB were even higher during the 1st week after birth than the corresponding maternal values. Symptoms of sedation were observed in these neonates for which elevated free-fraction values of PB could be responsible. Behavior problems, such as withdrawal symptoms, were observed in neonates who eliminated PMD with short half-lives, while other infants with longer PMD half-lives or slower elimination because of nursing showed no such symptoms.
Topics: Behavior; Epilepsy; Female; Half-Life; Humans; Infant, Newborn; Milk, Human; Phenobarbital; Primidone; Substance Withdrawal Syndrome
PubMed: 3383727
DOI: 10.1159/000457682 -
European Journal of Pharmacology Mar 1989In amygdala-kindled rats, single-dose administration of primidone did not reduced seizure activity 2 h after i.p. injection, i.e. when plasma levels of the drug were... (Comparative Study)
Comparative Study
In amygdala-kindled rats, single-dose administration of primidone did not reduced seizure activity 2 h after i.p. injection, i.e. when plasma levels of the drug were highest, but significant anticonvulsant effects were found 24 h after administration, when the drug was almost completely eliminated. During chronic treatment with primidone, marked anticonvulsant efficacy was determined after 3-15 days of three times daily treatment with 50 mg/kg i.p., indicating that this effect was due to the accumulation of metabolites, especially phenobarbital. Maximum anticonvulsant activity attained during chronic primidone medication was almost equal to that found during chronic treatment of kindled rats with phenobarbital, 30 mg/kg once daily. However, drug plasma level determinations during both treatments showed that on days when both treatments were about equieffective, levels of metabolically derived phenobarbital in the primidone group were significantly lower than levels in rats treated with phenobarbital alone, thus indicating that primidone potentiated the anticonvulsant effect of metabolically derived phenobarbital. Additional evidence for potentiation of the anticonvulsant effect of phenobarbital by primidone was found in single dose experiments with combined injection of both drugs, whereas side-effects, such as ataxia and muscle relaxation, induced by phenobarbital were not increased by combined treatment with primidone. Accordingly, side-effects occurring during chronic primidone treatment were less pronounced than side-effects found during chronic phenobarbital medication. In both treatment groups, tolerance to the anticonvulsant effect developed during the 2nd week of administration, while attenuation of side-effects took place already in the first week. Following cessation of treatment, signs of physical dependence, such as withdrawal hyperexcitability and weight loss, were observed. The data indicate that, at least in kindled rats, the anticonvulsant activity of primidone during chronic treatment is due to the combined and possibly synergistic actions of primidone and metabolically derived phenobarbital.
Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Electrodes, Implanted; Female; Kindling, Neurologic; Phenobarbital; Primidone; Rats; Rats, Inbred Strains; Seizures; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 2721568
DOI: 10.1016/0014-2999(89)90294-x