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Bollettino Chimico Farmaceutico Jun 1992Shelf-lives of liquid pharmaceutical preparations (injectable and oral solution) containing phenobarbital sodium, commercially available in Brazil, were predicted by...
Shelf-lives of liquid pharmaceutical preparations (injectable and oral solution) containing phenobarbital sodium, commercially available in Brazil, were predicted by accelerated stability test using isothermal method (at 37 degrees C, 50 degrees C and 75 degrees C). Data obtained in high temperature studies using Arrhenius relation were applied to predict shelf-lives at room temperature. The shelf-lives were calculated by linear regression analysis. UV difference spectrophotometry was used for phenobarbital determination. Thin-layer chromatography was used for separation and identification of phenylethylacethylurea, the main degradation product of phenobarbital.
Topics: Chromatography, Thin Layer; Drug Stability; Hydrolysis; Phenobarbital; Spectrophotometry, Ultraviolet
PubMed: 1445688
DOI: No ID Found -
The New England Journal of Medicine Sep 1982We investigated the effect of multiple oral doses of activated charcoal on the pharmacokinetics of intravenously administered phenobarbital in a randomized crossover... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
We investigated the effect of multiple oral doses of activated charcoal on the pharmacokinetics of intravenously administered phenobarbital in a randomized crossover trial. Six healthy men volunteered to take 200 mg of phenobarbital sodium per 70 kg of body weight intravenously on two separate occasions. On one occasion, each subject received oral activated charcoal (180 g) in divided doses over three days after the infusion of phenobarbital. Serum levels of phenobarbital were measured in all subjects up to 96 hours after the infusion, and urinary excretion of phenobarbital was measured in two subjects 24 to 96 hours after the infusion. A pharmacokinetic analysis showed that the charcoal decreased the serum half-life of phenobarbital form 110 +/- 8 to 45 +/- 6 hours (S.E.M.) (P less than 0.01), increased the total body clearance of phenobarbital from 4.4 +/- 0.2 to 12.0 +/- 1.6 ml per kilogram per hour (P less than 0.01), and increased the nonrenal clearance from 52 to 80 per cent of the total body clearance. We conclude that oral administration of activated charcoal enhances the nonrenal clearance of phenobarbital.
Topics: Administration, Oral; Adult; Charcoal; Clinical Trials as Topic; Humans; Infusions, Parenteral; Kinetics; Male; Phenobarbital; Random Allocation
PubMed: 7050705
DOI: 10.1056/NEJM198209093071102 -
American Journal of Hospital Pharmacy Feb 1986The stability of phenobarbital sodium diluted to 10 mg/mL in 0.9% sodium chloride injection was studied at an unadjusted pH (8.5) and an adjusted pH (10.0) at 4 degrees...
The stability of phenobarbital sodium diluted to 10 mg/mL in 0.9% sodium chloride injection was studied at an unadjusted pH (8.5) and an adjusted pH (10.0) at 4 degrees C over a four-week period. The phenobarbital concentrations were measured before dilution and at 1, 2, 3, 7, 14, and 28 days using high-performance liquid chromatography. The observed phenobarbital concentrations ranged from 98.0 to 106.0% of initial concentration at the unadjusted pH and from 96.7 to 108.5% of initial concentration at the adjusted pH. The diluted phenobarbital sodium was stable over a four-week period at 4 degrees C without the need for pH adjustment.
Topics: Drug Stability; Humans; Hydrogen-Ion Concentration; Infant; Injections; Phenobarbital; Sodium Chloride; Solutions; Time Factors
PubMed: 3953601
DOI: No ID Found -
Canadian Journal of Veterinary Research... Jan 1990Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay...
Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.
Topics: Administration, Oral; Animals; Cats; Female; Injections, Intravenous; Male; Phenobarbital
PubMed: 2306662
DOI: No ID Found -
Equine Veterinary Journal Jul 1984Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20... (Comparative Study)
Comparative Study
Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.
Topics: Animals; Animals, Newborn; Female; Half-Life; Horses; Kinetics; Male; Phenobarbital
PubMed: 6479136
DOI: 10.1111/j.2042-3306.1984.tb01946.x -
Journal of Immunological Methods 1979A radioimmunoassay for phenobarbital has been studied. Antiphenobarbital antisera were obtained by repeated immunization of rabbits with p-succinamidophenobarbital...
A radioimmunoassay for phenobarbital has been studied. Antiphenobarbital antisera were obtained by repeated immunization of rabbits with p-succinamidophenobarbital conjugated to bovine serum albumin. Less than 0.2 pmol of phenobarbital could be measured by this procedure. The specificity of the antibodies was directed to substituents on the nitrogen atoms of the barbituric ring as well as to substituents at the carbon 5-position of the ring.
Topics: Antibody Formation; Phenobarbital; Radioimmunoassay; Serum Albumin, Bovine
PubMed: 469270
DOI: 10.1016/0022-1759(79)90327-2 -
Pharmacotherapy 1997A 2.5-year-old child receiving phenobarbital for a history of seizures while on continuous cycling peritoneal dialysis (CCPD) had persistent subtherapeutic serum levels...
A 2.5-year-old child receiving phenobarbital for a history of seizures while on continuous cycling peritoneal dialysis (CCPD) had persistent subtherapeutic serum levels despite progressive dosage increases. Phenobarbital concentration was measured in the peritoneal dialysate effluent and peritoneal clearance was calculated. Thirty-five percent of the total phenobarbital daily dose was being removed through 24-hour CCPD. Our findings were consistent with previous reports of 40% and 50% phenobarbital removal during continuous ambulatory peritoneal dialysis and acute peritoneal dialysis, respectively. In addition, phenobarbital clearance was greater during the period when more exchanges were done compared with the period when patient went through one cycle with a longer dwell time. Based on these preliminary data, it seems that larger dosages of phenobarbital are necessary in patients undergoing continuous peritoneal dialysis, and that the amount removed can differ significantly depending on the number of cycles.
Topics: Anticonvulsants; Child, Preschool; Dialysis Solutions; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Phenobarbital; Seizures
PubMed: 9250568
DOI: No ID Found -
Journal of Clinical Pharmacology 1979Serum levels of phenobarbital, and also urinary excretion of phenobarbital and p-hydroxyphenobarbital, were examined after single and repeated oral doses of...
Serum levels of phenobarbital, and also urinary excretion of phenobarbital and p-hydroxyphenobarbital, were examined after single and repeated oral doses of phenobarbital to three male subjects. Serum levels of phenobarbital at steady state were approximately ten times as high as those after a single dose. The overall elimination rate constant for loss of phenobarbital from serum, Kel, was significantly reduced after repeated doses, and Cmax infinity values calculated from single-dose data poorly predicted observed Cmax infinity values. Five-day urinary excretion of phenobarbital and p-hydroxyphenobarbital accounted for 16 and 21 per cent, respectively, of the initial dose. Due to extensive drug accumulation, 83 per cent of the final dose was excreted in five-day urine as phenobarbital and 85 per cent, as p-hydroxyphenobarbital. Comparison of plasma and renal clearances indicated that the rate of phenobarbital metabolism was reduced owing to repeated dosing, while the rate of urinary excretion of parent drug was unchanged.
Topics: Adult; Half-Life; Humans; Hydroxylation; Kinetics; Male; Phenobarbital; Time Factors
PubMed: 469023
DOI: 10.1002/j.1552-4604.1979.tb02481.x -
American Journal of Veterinary Research May 1992Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive... (Comparative Study)
Comparative Study
Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartment model. Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24.2 +/- 4.7 and 11.2 +/- 2.3 hours, volume of distribution = 0.960 +/- 0.060 and 0.914 +/- 0.119 L/kg, and clearance = 28.2 +/- 5.1 and 57.3 +/- 9.6 ml/h/kg, respectively. Results indicated that significant (P less than 0.05) difference in half-life and oral clearance existed between single and repeated dosing. The significant decrease in half-life after repeated dosing with phenobarbital may be indicative of enzyme induction. Significant difference was not observed between baseline serum enzyme concentration and concentration measured on day 42, except for gamma-glutamyltransferase activity, which was significantly increased on day 42 in 3 of the 6 horses. On the basis of increases in oral clearance observed over 42 days, dose adjustments may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Absorption; Administration, Oral; Animals; Half-Life; Horses; Liver; Phenobarbital; Tissue Distribution
PubMed: 1524295
DOI: No ID Found -
Developmental Pharmacology and... 1991Steady-state plasma phenobarbital (PB) concentrations (n = 671) were measured in 438 inpatients. There was a significant relationship between age and PB dose ratio...
Steady-state plasma phenobarbital (PB) concentrations (n = 671) were measured in 438 inpatients. There was a significant relationship between age and PB dose ratio (concentration/dose or 1/clearance) for monotherapy patients; the dose ratio declined in the first year of life, but the dose ratio increased after age 1. The dose ratios were significantly higher in patients receiving PB in combination with other antiepileptic drugs. However, neither sex nor formulations used (tablet, elixir and intravenous) had any influence on the PB dose ratio. The age-dose-concentration relationships indicate that children, especially those under 11 years of age, may require maintenance PB doses more than 5 mg/kg/day to achieve the commonly recommended 'therapeutic' concentration range (10-40 mg/l).
Topics: Adolescent; Adult; Aging; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Epilepsy; Female; Humans; Infant; Infant, Newborn; Male; Phenobarbital
PubMed: 1811924
DOI: 10.1159/000457502