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Epilepsia Dec 2012
Topics: Anticonvulsants; Epilepsy; History, 20th Century; History, 21st Century; Humans; Phenobarbital
PubMed: 23205957
DOI: 10.1111/epi.12023 -
Epilepsia Dec 1975Diphenylhydantoin, primidone, and phenobarbital were determined in saliva and plasma of 164 patients by gas-liquid chromatography. The saliva ratio was about one-tenth...
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.
Topics: Humans; Kinetics; Phenobarbital; Phenytoin; Primidone; Saliva
PubMed: 1222748
DOI: 10.1111/j.1528-1157.1975.tb04758.x -
Journal of Pharmacological and... 2021Administration of a compound can induce drug-metabolizing enzymes (DMEs) in the liver. DME induction can affect various parameters in toxicology studies. Therefore,...
Quantitative protein profiling of phenobarbital-induced drug metabolizing enzymes in rat liver by liquid chromatography mass spectrometry using formalin-fixed paraffin-embedded samples.
Administration of a compound can induce drug-metabolizing enzymes (DMEs) in the liver. DME induction can affect various parameters in toxicology studies. Therefore, evaluation of DME induction is important for interpreting test compound-induced biological responses. Several methods such as measurement of hepatic microsomal DME activity using substrates, electron microscopy, or immunohistochemistry have been used; however, these methods are limited in throughput and specificity or are not quantitative. Liquid chromatography mass spectrometry (LC/MS)-based protein analysis can detect and quantify multiple proteins simultaneously per assay. Studies have shown that formalin-fixed paraffin-embedded (FFPE) samples, which are routinely collected in toxicology studies, can be used for LC/MS-based protein analysis. To validate the utility of LC/MS using FFPE samples for quantitative evaluation of DME induction, we treated rats with a DME inducer, phenobarbital, and compared the protein expression levels of 13 phase-I and 11 phase-II DMEs between FFPE and fresh frozen hepatic samples using LC/MS. A good correlation between data from FFPE and frozen samples was obtained after analysis. In FFPE and frozen samples, the expression of 6 phase-I and 8 phase-II DMEs showed a similar significant increase and a prominent rise in Cyp2b2 and Cyp3a1 levels. In addition, LC/MS data were consistent with the measurement of microsomal DME activities. These results suggest that LC/MS-based protein expression analysis using FFPE samples is as effective as that using frozen samples for detecting DME induction.
Topics: Animals; Chromatography, Liquid; Enzymes; Liver; Paraffin Embedding; Phenobarbital; Proteomics; Rats; Tandem Mass Spectrometry; Tissue Fixation
PubMed: 34363961
DOI: 10.1016/j.vascn.2021.107107 -
Acta Paediatrica Scandinavica Mar 1978Two adult volunteers and four newborn infants were given a single dose of phenobarbital. The output in the urine o f unchanged phenobartital and of the two main...
Two adult volunteers and four newborn infants were given a single dose of phenobarbital. The output in the urine o f unchanged phenobartital and of the two main metabolites p-hydroxy phenobarbital and conjugated p-hydroxy phenobarbital was followed during 8 days in the newborns and during 2 or 4 weeks in the adults. The plasma levels were also determined and some pharmacokinetic constants calculated. It was found that the newborn patients excreted unchanged phenobartibal and p-hydroxy phenobarbital in the same proportions relative to dose as did the adult volunteers, 2.e. 16--17% unchanged drug and 9--10% of the metabolite during the first 8 days after administration. On the other hand, there was a clear-cut age difference in output of conjugated metabolite where the newborns excreted only 5% of the given dose during the 8-day observation period. The corresponding value for the adults was 15%. It is concluded that a poor conjugating capacity in the newborn may not have any serious consequences with a drug like phenobarbital where major alternative routes of excretion exist (unchanged drug and unconjugated metabolite). The clinical significance of immature drug metabolites and of unchanged drug is taken into consideration.
Topics: Adult; Age Factors; Female; Humans; Infant, Newborn; Male; Phenobarbital
PubMed: 626078
DOI: 10.1111/j.1651-2227.1978.tb16302.x -
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 -
Acta Paediatrica Scandinavica May 1975The plasma concentration of phenobarbital given as anticonvulsive treatment in the newborn period has been followed in 18 infants. With constant daily doses, the drug... (Comparative Study)
Comparative Study
The plasma concentration of phenobarbital given as anticonvulsive treatment in the newborn period has been followed in 18 infants. With constant daily doses, the drug accummulated for at least 5 days. After intramuscular injection of a single dose, 90% of the peak concentration was reached within 4 hours in 8 of the 10 infants. The peak concentration (in mug/ml) approximately equalled 1.3 x the dose (in mg/kg). Absorption after oral administration was less reliable. In 12 of the infants the clinical course allowed attempts to evaluate the anticonvulsive effect of phenobarbital. In 4 cases the convulsions continued. In those 8 infants where phenobarbital seemed to be effective, the approximate range of phenobarbital concentration when convulsions ceased was 12-30 mug/ml. Phenobarbital half-life ranged between 59 and 182 hours. In some infants the rate of phenobarbital disappearance from the plasma varied considerably from day to day. The pathological conditions causing seizures probably influence the distribution, metabolism and excretion of the drug. For the often seriously ill infants with convulsions it is therefore difficult to construct rational maintenance dose schedules, and optimal dosage must be based on repeated determinations of the plasma concentration.
Topics: Administration, Oral; Diazepam; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Infant, Premature; Injections, Intramuscular; Lidocaine; Male; Phenobarbital; Seizures; Tablets
PubMed: 1155069
DOI: 10.1111/j.1651-2227.1975.tb03873.x -
Pediatric Clinics of North America Feb 1972
Review
Topics: Animals; Anticonvulsants; Child; Drug Interactions; Electroencephalography; Ethosuximide; Half-Life; Humans; Liver; Mephobarbital; Phenobarbital; Phenytoin; Primidone
PubMed: 4558884
DOI: 10.1016/s0031-3955(16)32675-x -
Journal of Clinical Pharmacy and... Aug 1993Owing to the changes occurring in the organism as a result of biological maturation, disposition kinetics of phenobarbital in newborns is significantly different to that...
Owing to the changes occurring in the organism as a result of biological maturation, disposition kinetics of phenobarbital in newborns is significantly different to that observed in the paediatric and adult populations. Moreover, the disposition parameters change constantly during the first days of life. The data on the serum levels of phenobarbital in 17 newborns were analysed to quantify the changes in the elimination half-life of phenobarbital during the first weeks of life. The half-life of the drug was estimated to be (mean +/- SD) 114.2 +/- 43.0 h, 73.19 +/- 24.17 h and 41.23 +/- 13.95 h in patients 1-10, 11-30 and 31-70 days old, respectively. According to these values and assuming phenobarbital serum levels of 20 mg/l to be safe and effective in neonatal seizures, the initial dosing recommended is 2.9, 4.8 and 6.0 mg/kg/day in newborns 1-10, 11-30 and 31-70 days old, respectively.
Topics: Drug Administration Schedule; Humans; Infant; Infant, Newborn; Models, Biological; Phenobarbital; Seizures
PubMed: 8227234
DOI: 10.1111/j.1365-2710.1993.tb00586.x -
Chemical & Pharmaceutical Bulletin Nov 1980
Topics: Animals; Cattle; Immunoenzyme Techniques; Phenobarbital
PubMed: 7011583
DOI: 10.1248/cpb.28.3291 -
Psychosomatics 1974
Clinical Trial
Topics: Administration, Oral; Adult; Anxiety Disorders; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Phenobarbital; Placebos; Probability
PubMed: 4606925
DOI: 10.1016/S0033-3182(74)71291-9