Primidone-induced hyperammonemic encephalopathy in a patient with cerebral astrocytoma
19
Citation
7
Reference
10
Related Paper
Citation Trend
Keywords:
Primidone
Somnolence
Phenobarbital
After a dose of 400 mg/kg p.o. of primidone, 4% was excreted as phenobarbital whereas ethylphenylmalondiamide and primidone accounted for 48 and 20%, respectively. With multiple doses of primidone, increasing excretion of phenobarbital indicated that phenobarbital was accumulating in the animal. This effect occurred because of slow excretion of the phenobarbital and could not have resulted from accumulation of primidone or gradual increased absorption of the oral doses of primidone. Since the original estimate of 4% conversion of primidone to phenobarbital was based solely on measurement of free phenobarbital, the further metabolism of phenobarbital itself was studied. With phenobarbital-2-C 14 i.v., results indicated that about 40% of the urinary radioactivity was free phenobarbital with a small amount of free p -hydroxyphenobarbital. The major metabolite in the rabbit was presumably p -hydroxyphenobarbitalglucuronide as indicated by countercurrent analyses and ability to be hydrolyzed by β-glucuronidase. In these studies with phenobarbital-2-C 14 , a circadian rhythm was manifested in the percentage of the radioactivity excreted as phenobarbital and the metabolite.
Primidone
Phenobarbital
Cite
Citations (23)
Primidone
Phenobarbital
Cite
Citations (9)
SummaryPrimidone (Mysoline) is in part converted to phenobarbital by dog and by man. Concentrations of phenobarbital found in plasma of patients receiving therapeutic doses of primidone are high enough to exert a significant antiepileptic effect.
Primidone
Phenobarbital
Cite
Citations (69)
Children were treated for epilepsy with phenobarbital and diphenylhydantoin. In 2 cases, diphenylhydantoin could not be detected in the serum when combined with doses of phenobarbital above 1 mg. per kilogram per day. Other cases showed either a lowering of hydantoin levels or no change in the presence of phenobarbital. A method is presented which permits the quantitation of these two drugs and primidone from the same 0.5 ml. sample of serum. Serum half‐life of phenobarbital in 6 children was in the range of 37 to 73 hours. This is a lower range than that published for adults
Phenobarbital
Primidone
Serum concentration
Cite
Citations (78)
Primidone
Phenobarbital
Liter
Cite
Citations (16)
THe effects of phenobarbital on the plasma concentration of phenytoin and mortality of the phenytoin-treated mice were mainly studied. The plasma concentration of phenytoin estimated in the live mice after electroshock was significantly higher than that in the dead mice, suggesting that biological activity of phenytoin is dependent on its plasma concentration where individual difference seems to be large. Though the pretreatment of mice with phenobarbital lowered the plasma concentration of phenytoin, all the mice were alive after electroshock with further treatment with phenobarbital and phenytoin. These results suggest that combination of phenobarbital with phenytoin for the treatment of epileptic patients may be feasible.
Phenobarbital
Cite
Citations (0)
Primidone
Phenobarbital
Cite
Citations (7)
Schwartz‐Porsche, D., Löscher, W. & Frey, H.‐H. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J. vet. Pliannacol. Therap. 8, 113–119. 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 5‐17mg/kg phenobarbital and from 17‐70mg/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. Dr H.‐H. Frey, Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstrafie 20, D‐1000 Berlin‐West 33, Germany.
Primidone
Phenobarbital
Cite
Citations (107)
Primidone
Phenobarbital
Cite
Citations (0)
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.
Primidone
Phenobarbital
Dose
Serum concentration
Therapeutic index
Cite
Citations (71)