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Journal of the American Veterinary... May 1984Serum concentrations, drug dosages, and seizure control were monitored in 142 dogs on a variety of anticonvulsant treatment regimens, using phenytoin, primidone, and...
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.
Topics: Animals; Dog Diseases; Dogs; Drug Therapy, Combination; Epilepsy; Phenobarbital; Phenytoin; Primidone
PubMed: 6725128
DOI: No ID Found -
Parkinsonism & Related Disorders Oct 2003Essential tremor is the most common involuntary movement; we studied 113 affected subjects (54 men, 59 women) with an average age of 63.9 years and average duration of... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Essential tremor is the most common involuntary movement; we studied 113 affected subjects (54 men, 59 women) with an average age of 63.9 years and average duration of 9.05 years. These patients participated in a double-blind study with a 1-year follow-up to compare treatment efficiency using primidone dosages of 250 mg/day (G 250, 56 patients) versus 750 mg/day (G 750, 57 patients). The study was designed with an 80% power and 95% confidence level. The statistical analysis used was an ANOVA (with Bonferroni multiple comparison test corrections); a value of p<0.004 was accepted as significant. To compare other values, a chi-square test was used; p<0.05 was considered significant. To evaluate the efficacy of the drug, clinical protocol employed the 'clinical evaluation scale for tremor'. All of the patients were evaluated a total of 13 times, once prior to the introduction of primidone and the other 12 evaluations following the initiation of the treatment. Eighty-seven patients completed the study: 15 patients abandoned the study due to undesirable side effects, five due to negative response, and six who were lost to follow-up. The percentage of patients who didn't complete the study was significantly higher in the group that received 750 mg/day of primidone (p<0.04) and more frequent as well in this same group, due to undesirable side effects (p<0.03). The patients of both G250 and G750 showed a significant improvement in each of the controls compared to the basal value (p<0.0001). No significant differences (p<0.06) were found when the averages of the evaluations of each group were compared. These responses were maintained during the entire treatment period. Low doses of primidone (250 mg/day) were equally or more effective than high doses (750 mg/day) in the control of essential tremor; this response was maintained for 12 months and furthermore, demonstrated fewer undesirable effects.
Topics: Administration, Oral; Aged; Analysis of Variance; Chi-Square Distribution; Confidence Intervals; Disease Management; Double-Blind Method; Essential Tremor; Female; Follow-Up Studies; Humans; Male; Middle Aged; Primidone
PubMed: 14499204
DOI: 10.1016/s1353-8020(03)00070-1 -
European Journal of Drug Metabolism and... 1999Primidone is a clinically useful antiepileptic drug that is metabolised to two pharmacologically active metabolites phenobarbital and phenylethylmalonamide. As data on...
Primidone is a clinically useful antiepileptic drug that is metabolised to two pharmacologically active metabolites phenobarbital and phenylethylmalonamide. As data on the inter-relationship between the systemic and central nervous system pharmacokinetics of primidone and its metabolites are sparse, we have investigated their temporal inter-relationship using a freely behaving rat model which allows repeated sampling of blood (100 microl) and cerebrospinal fluid (CSF; 20 microl). After administration, by intraperitoneal injection (50, 100 or 200 mg/kg), primidone rapidly appeared in both serum (Tmax mean range 1.5-2.5 h) and CSF (Tmax mean range 2.0-3.5 h), suggesting ready penetration of the blood-brain-barrier. This was also the case for phenylethylmalonamide and phenobarbital but peak concentration occurred later. Primidone, phenylethylmalonamide and phenobarbital concentrations rose linearly and dose-dependently in both serum and CSF. The mean free fraction (free/total concentration ratio) for primidone, phenylethylmalonamide and phenobarbital was 0.86, 0.97 and 0.88, respectively, and, as their respective mean CSF/serum ratio values were 0.73, 1.06 and 0.65, it would suggest that equilibration between the blood and CSF compartments is rapid. CSF mean t(1/2) values for primidone, phenylethylmalonamide and phenobarbital were similar to those of sera and essentially paralleled the pattern seen in sera.
Topics: Animals; Half-Life; Male; Phenobarbital; Phenylethylmalonamide; Primidone; Rats; Rats, Sprague-Dawley
PubMed: 10716065
DOI: 10.1007/BF03190029 -
Journal of Biomolecular Structure &... 2015Primidone (Mysoline), with the chemical formula 5-ethyl-5-phenyl-hexahydropyrimidine- 4,6-dione (C12H14N2O2), has been a valuable drug in the treatment of epilepsy. In...
Primidone (Mysoline), with the chemical formula 5-ethyl-5-phenyl-hexahydropyrimidine- 4,6-dione (C12H14N2O2), has been a valuable drug in the treatment of epilepsy. In the present work, the experimental IR and Raman spectra of solid phase primidone were recorded, and the results were compared with theoretical wavenumber values of monomer and dimer forms of the title molecule. Vibrational spectral simulations in the dimer form were carried out to improve the assignment of the bands in the solid phase experimental spectra. The possible stable conformers of free molecule were searched by means of torsion potential energy surfaces scan studies through two dihedral angles. The molecular geometries of the monomer and dimer forms of title molecule were optimized using DFT method at B3LYP/6-31++G(d,p) level of theory. Using PEDs determined the contributions of internal (stretching, bending, etc.) coordinates to each normal mode of vibration. Further, HOMO-LUMO energy gap and NBO properties of the investigated molecule in monomer and dimer forms were also calculated.
Topics: Anticonvulsants; Hydrogen Bonding; Models, Chemical; Models, Molecular; Molecular Conformation; Primidone; Quantum Theory; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Thermodynamics
PubMed: 24712318
DOI: 10.1080/07391102.2014.913505 -
British Medical Journal (Clinical...
Clinical Trial Randomized Controlled Trial
Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Humans; Middle Aged; Primidone; Random Allocation; Tremor
PubMed: 6819034
DOI: 10.1136/bmj.285.6342.608 -
European Journal of Clinical... Oct 1975Plasma, brain, lumbar CSF, skeletal muscle, skin and bone concentrations of phenytoin, phenobarbitone and primidone have been measured in specimens from patients... (Comparative Study)
Comparative Study
Plasma, brain, lumbar CSF, skeletal muscle, skin and bone concentrations of phenytoin, phenobarbitone and primidone have been measured in specimens from patients undergoing temporal lobectomy for chronic epilepsy. A good correlation was found between the plasma and brain concentrations of each drug. Similarly, a good correlation was found between the plasma and CSF concentrations of each drug. Assuming that CSF is an ultrafiltrate of plasma, the percentage of phenytoin, phenobarbitone and primidone which was unbound in plasma was 10-14%, 43% and 81% respectively. Skeletal muscle concentrations of phenytoin and phenobarbitone and the skin concentration of phenytoin, also correlated with the plasma concentrations, but the remaining tissues did not give significant correlations.
Topics: Adolescent; Adult; Brain Chemistry; Child; Child, Preschool; Chromatography, Gas; Epilepsy, Temporal Lobe; Humans; Phenobarbital; Phenytoin; Primidone
PubMed: 1233256
DOI: 10.1007/BF00613432 -
Annals of Emergency Medicine Jun 1999
Topics: Anticonvulsants; Crystallization; Cysteine; Drug Monitoring; Emergency Treatment; Female; Humans; Middle Aged; Primidone
PubMed: 10339696
DOI: 10.1016/s0196-0644(99)80022-5 -
Pediatric Annals Jan 1993
Review
Topics: Adrenergic beta-Antagonists; Child; Humans; Primidone; Tremor
PubMed: 8094242
DOI: 10.3928/0090-4481-19930101-10 -
The Journal of Neuroscience Nursing :... Jun 1991Tremor is a rhythmic, involuntary muscular contraction with consistency of rate, amplitude and pattern. It is the most common of all involuntary movements. Several...
Tremor is a rhythmic, involuntary muscular contraction with consistency of rate, amplitude and pattern. It is the most common of all involuntary movements. Several systems for classifying tremor exist with the most frequent system classed according to behavioral context, ie, resting, postural and action. Clinical recognition of tremor type is extremely important as type determines prognosis, treatment and need for genetic counseling. The most common forms are parkinsonian, physiological, cerebellar intention and essential tremor. Essential or hereditary tremor is the most common of all neurologic conditions with 3-4 million Americans affected. Nursing implications of caring for essential tremor patients are presented.
Topics: Adrenergic beta-Antagonists; Humans; Patient Care Planning; Primidone; Tremor
PubMed: 1678770
DOI: 10.1097/01376517-199106000-00007 -
Journal of Neurology Jun 1975Little is known about the influence of phenytoin and ethosuximide on primidone. Therefore we studied three groups of patients: 28 receiving primidone alone, 16 on...
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.
Topics: Drug Interactions; Drug Therapy, Combination; Epilepsy; Ethosuximide; Female; Humans; Male; Phenobarbital; Phenytoin; Primidone; Saliva
PubMed: 51048
DOI: 10.1007/BF00314604