Neonatal Phenobarbital and Phenytoin Binding Profiles

Painter, Michael J.; Minnigh, M. Beth; Gaus, Lisa M.; Scher, Mark S.; Brozanski, Beverly; Alvin, John

doi:10.1002/j.1552-4604.1994.tb01999.x

Cited by 23 publications

(8 citation statements)

References 10 publications

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“…8 It also requires frequent blood-level monitoring, and is not an ideal medication for maintenance at discharge given its erratic oral absorption, frequency of dosing (usually every 6-8 hours), and continuing drug metabolism changes in young infants. 8,38,39 Blood loss due to therapeutic drug monitoring may be benign in older patients, but is potentially harmful and increases the risk of transfusion and associated morbidities/mortality in neonates whose blood volumes average 80 mL/kg. [40][41][42][43][44][45] Levetiracetam appeared to acutely reduce seizure burden in 2 separate studies, but there were no within-study comparison groups.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Treatment of Neonatal Seizures

2013

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Pharmacologic treatment options for neonatal seizures have expanded over the last two decades and there is no consensus on optimal treatment strategy. We systematically reviewed the published literature to determine which medication(s) are most effective for treating neonatal seizures, by retrieving trials and observational investigations via PubMed (through August 2011) that focused on pharmacological seizure treatment of neonates (≤ 28 days old) and utilized continuous or amplitude-integrated EEG to confirm seizure diagnosis and cessation. Our search identified 557 initial articles and 14 additional studies after reference reviews, with 16 meeting inclusion criteria. Two were randomized trials and only three additional investigations included comparison groups. We found limited evidence regarding the best pharmacologic treatment for neonatal seizures, but were able to devise a treatment algorithm from available data. These findings have the potential to serve both as a clinical reference and inform the design of comparative effectiveness investigations for neonatal antiepileptics.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Treatment of Neonatal Seizures

2013

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“…[12][13][14][15][16] Furthermore, elevated glycated albumin concentrations, hyperlipidemia, hyperbilirubinemia, and concomitant use of valproic acid or carbamazepine can cause protein displacement of phenytoin, thereby increasing the unbound concentrations. 12,[17][18][19][20][21][22][23][24][25] However, all these possible covariates for the protein binding of phenytoin have mostly been univariately investigated in small, and often adult, populations. Previously identified covariates for protein binding of phenytoin in adults could not necessarily apply to children.…”

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confidence: 99%

The Quantitative Effect of Serum Albumin, Serum Urea, and Valproic Acid on Unbound Phenytoin Concentrations in Children

et al. 2013

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Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity.

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“…However, in the case of theophylline, the response in the blood is relatively less than the response in the buffer. The ratio of binding of theophylline with serum protein (40%) is not significantly larger than that of VCM (34%) or phenobarbital (20–45%); thus, it is unlikely that the protein binding decreases the sensitivity in blood [ 40 , 41 , 42 , 43 , 44 , 45 ]. The lower sensitivity to theophylline is probably due to the interaction of some coexistence in blood resulted from the insufficient specificity of the MIP comparing with other MIPs is this work.…”

Section: Resultsmentioning

confidence: 99%

A “Single-Use” Ceramic-Based Electrochemical Sensor Chip Using Molecularly Imprinted Carbon Paste Electrode

Aaryashree

Takeda

Kanai

et al. 2020

Sensors

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An inexpensive disposable electrochemical drug sensor for the detection of drugs (vancomycin, meropenem, theophylline, and phenobarbital) is described. Molecularly imprinted polymer (MIP) templated with the target drugs was immobilized on the surface of graphite particles using a simple radical polymerization method and packed into the working electrode of a three-electrode ceramic-based chip sensor. Differential pulse voltammetry (DPV) was used to determine the relationship between the response current and the concentration of the targeted drug while using one sensor chip for one single operation. The time required for each DPV measurement was less than 2 min. Concentrations corresponding to the therapeutic range of these drugs in plasma were taken into account while performing DPV. In all the cases, the single-used MIP sensor showed higher sensitivity and linearity than non-imprinted polymer. The selectivity test in drugs with a structure similar to that of the target drugs was performed, and it was found that MIP-based sensors were more selective than the untreated ones. Additionally, the test in whole blood showed that the presence of interfering species had an insignificant effect on the diagnostic responses of the sensor. These results demonstrate that the disposable MIP-sensor is promising for quick and straightforward therapeutic drug monitoring to prevent the toxic side effects and the insufficient therapeutic effect due to the overdose and underdose, respectively.

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Neonatal Phenobarbital and Phenytoin Binding Profiles

Cited by 23 publications

References 10 publications

Pharmacological Treatment of Neonatal Seizures

Pharmacological Treatment of Neonatal Seizures

The Quantitative Effect of Serum Albumin, Serum Urea, and Valproic Acid on Unbound Phenytoin Concentrations in Children

A “Single-Use” Ceramic-Based Electrochemical Sensor Chip Using Molecularly Imprinted Carbon Paste Electrode

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