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Drug Intelligence & Clinical Pharmacy Oct 1982
Review
Topics: Binding, Competitive; Drug Interactions; Half-Life; Humans; Kinetics; Phenobarbital; Phenytoin; Protein Binding; Seizures; Valproic Acid
PubMed: 6814881
DOI: 10.1177/106002808201601002 -
Perfusion May 2018The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants.
INTRODUCTION
The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants.
METHODS
The aim of the study was to evaluate the individual pharmacokinetics (PK) of phenobarbital and the effect of PK covariates in neonates and infants undergoing ECMO. Sixteen patients (7 neonates, 9 infants) treated with phenobarbital during ECMO (centrifugal-flow pump circuits) were enrolled in the PK study. Phenobarbital serum concentrations were measured using a fluorescence polarization immunoassay. Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model.
RESULTS
The mean (SD) Vd and CL values in neonates were 0.46 (0.24) L/kg and 8.0 (4.5) mL/h/kg, respectively. Respective values in infants were 0.56 (0.23) L/kg and 8.5 (3.1) mL/h/kg. PK parameters in neonates and infants were not significantly different. We observed high inter-individual variability in PK parameters (coefficients of variation [CV] were 52% and 53% for CL and Vd, respectively). Doses were adjusted based on therapeutic drug monitoring (TDM) in 87.5% patients. Only 50% of the first measured phenobarbital serum concentrations in each patient were within the therapeutic range of 10-40 mg/L, in comparison with 88.6% concentration measured after TDM implementation. Linear regression models showed that both Vd and CL are significantly related with body weight (BW) and length. Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively.
CONCLUSIONS
Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO.
Topics: Extracorporeal Membrane Oxygenation; Female; Humans; Infant; Infant, Newborn; Male; Phenobarbital
PubMed: 29788839
DOI: 10.1177/0267659118766444 -
The American Journal of Emergency... Feb 2020The purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute...
OBJECTIVE
The purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute management of alcohol withdrawal syndrome (AWS).
METHODS
This was a retrospective chart review of adult patients who presented to the Emergency Department with moderate or severe symptoms of alcohol withdrawal. Patients were included if they received at least 4 mg of lorazepam through the hospital's Alcohol Withdrawal Order Set on hospital day one. Patients who received a single parenteral dose of phenobarbital on hospital day one were compared to those who did not.
RESULTS
Forty patients received phenobarbital and 38 patients received lorazepam only. Median daily lorazepam requirements, disposition, hospital length of stay, and median maximum daily CIWA-Ar scores were not statistically significant different between the groups. Significantly more patients in the phenobarbital group were discharged within three days in comparison to the lorazepam only group (9 patients vs. 2 patients, respectively, p < 0.05). In the lorazepam only group, two patients were intubated, one patient had delirium tremens, and no patients seized. In the phenobarbital group no adverse events were observed.
CONCLUSIONS
More patients were discharged within three days if they received a single parenteral dose of phenobarbital on hospital day one, in addition to symptom-triggered lorazepam for the acute management of AWS. Emergency Medicine physicians should consider ordering one parenteral phenobarbital dose on hospital day one to patients presenting with AWS.
Topics: Adult; California; Female; Humans; Lorazepam; Male; Middle Aged; Phenobarbital; Retrospective Studies; Substance Withdrawal Syndrome
PubMed: 30744913
DOI: 10.1016/j.ajem.2019.01.053 -
Journal of the European Academy of... Oct 2017
Review
Topics: Child; Child, Preschool; Drug Eruptions; Female; Fever; Humans; Male; Phenobarbital; Suppositories
PubMed: 28380244
DOI: 10.1111/jdv.14261 -
Clinical Pediatrics Dec 1971
Topics: Drug Interactions; Female; Humans; Hyperbilirubinemia; Infant, Newborn; Jaundice, Neonatal; Phenobarbital; Pregnancy; Steroids; Substance-Related Disorders
PubMed: 5168664
DOI: 10.1177/000992287101001202 -
Neurotoxicology 1986Phenobarbital appears to produce similar behavioral effects on mice and humans with excitation at low and sedation or depression at higher doses. If plasma...
Phenobarbital appears to produce similar behavioral effects on mice and humans with excitation at low and sedation or depression at higher doses. If plasma concentrations of phenobarbital reflect levels in other tissue, then brain concentrations producing excitation (near 10 micrograms/g) and depression (near 20 micrograms/g) are not substantially different for the two species. The doses needed to produce these levels are much higher in mice than man. Plasma concentrations of phenobarbital decline during pregnancy in humans. Whether this decline is accompanied by increased seizure frequency has not been confirmed empirically and whether pregnancy influences the frequency of seizures at all is controversial. The reduction in phenobarbital levels in plasma or serum during pregnancy has been confirmed in rodents. Two of these studies however reported no difference brain concentrations of the drug during pregnancy. One study indicated increased potency of the drug, however this was not confirmed by the other two reports. The effects of phenobarbital on the progression of pregnancy and on offspring is not well defined in humans partly because the disease and the treatment effects are confounded. There are a few studies however which suggest that the effects might be drug specific. Animal studies in this area differ substantially from humans in design making any comparison tentative. The effects of the drug on pregnancy and neonates in rodents depends on the method of administering the drug and dose. Drug administration via the diet can provide high blood levels in the dams and causes lowered birthweight as well as several anatomical and hormonal abnormalities in offspring. This procedure, however, also severely reduced food intake and weight gains during pregnancy which might confound drug effects with nutritional deficiency. The drug can be injected in doses which produce plasma levels well within the therapeutic range for humans. Under these conditions the drug is less detrimental to the progression of pregnancy, however, the higher doses can increase neonatal mortality and reduce body weight of surviving offspring. Although mortality and body weight are not adversely effected by lower doses, changes are still apparent in the behavior as well as several biochemical parameters. Fostering studies on animals suggest that the effects of maternal injections of phenobarbital on offspring are due to the IN UTERO exposure rather than postnatal maternal factors and that effects produced by fostering itself may be confounded with the drug effects.
Topics: Animals; Brain Chemistry; Diet; Female; Humans; Kinetics; Litter Size; Mice; Motor Activity; Phenobarbital; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors; Tissue Distribution
PubMed: 3785754
DOI: No ID Found -
Journal of Pharmaceutical Sciences Mar 1962
Topics: Humans; Phenobarbital
PubMed: 13921369
DOI: 10.1002/jps.2600510306 -
Journal of Child Neurology Feb 2012This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates...
This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates treated with phenobarbital for clinical indications within 4 to 6 hours of clinically indicated collection of serum phenobarbital levels. Urine samples were also collected from control neonates not treated with phenobarbital. One aliquot was assayed fresh, another frozen at -30°C and assayed 1 to 3 months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi automated clinical chemistry analyzer. Serum and urine concentrations were compared as were fresh and frozen urine measurements. Serum phenobarbital ranged from 5.6 to 52.7 μg/mL. Matched urine samples were 56.6 ± 12.5% of the serum level. Frozen samples were 98.3 ± 8.0% of the fresh samples. Urine phenobarbital concentrations, either fresh or frozen, can be used in neonates as a noninvasive estimate of drug levels.
Topics: Epilepsy; Humans; Infant, Newborn; Medication Adherence; Phenobarbital
PubMed: 21954428
DOI: 10.1177/0883073811416665 -
Clinical Neurophysiology : Official... Oct 2016Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the...
OBJECTIVE
Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates.
METHODS
The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared.
RESULTS
Post-phenobarbital seizures showed significantly lower amplitude (p<0.001) and involved fewer EEG channels at the peak of seizure (p<0.05). No other features or SDA detection rates showed a statistical difference.
CONCLUSION
These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes.
SIGNIFICANCE
The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration.
Topics: Anticonvulsants; Electroencephalography; Epilepsy, Benign Neonatal; Humans; Infant, Newborn; Phenobarbital
PubMed: 27514722
DOI: 10.1016/j.clinph.2016.07.007 -
The Journal of Pediatrics Mar 1979
Topics: Child; Cholestasis; Chronic Disease; Humans; Phenobarbital
PubMed: 423047
DOI: 10.1016/s0022-3476(79)80616-2