Plasma Concentrations of Phenobarbital in the Treatment of Seizures in Newborns

Jalling, Birgitta

doi:10.1111/j.1651-2227.1975.tb03873.x

Cited by 60 publications

(31 citation statements)

References 10 publications

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“…All the children achieved plasma phenobarbital concentrations of greater than 10 mg l −1 within 10 min after the loading dose, and peak phenobarbital plasma concentrations of greater than 15 mg l −1 . Mean clearance, steady state volume of distribution, fraction unbound and CSF:plasma ratio were comparable to reported values in paediatric patients [11,[15][16][17], whereas the mean elimination half-life was comparable to values previously reported in children with severe malaria [4].…”

Section: Discussionsupporting

confidence: 67%

Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

Kokwaro

Ogutu

Muchohi

et al. 2003

Brit J Clinical Pharma

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Aims Phenobarbital is commonly used to treat status epilepticus in resource‐poor countries. Although a dose of 20 mg kg−1 is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15‐mg kg−1 intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus.Methods Twelve children (M/F: 11/1), aged 7–62 months, received a loading dose of phenobarbital (15 mg kg−1) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg−1 at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l−1 for 72 h.Results All the children achieved plasma concentrations above 15 mg l−1 by the end of the infusion. Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, ∞) ]: 4259 (3169, 5448) mg l−1.h, : 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg−1 h−1, Vss: 0.8 (0.7, 0.9) l kg −1, CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n= 6) and Cmax: 19.9 (17.9–27.9) mg l−1. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg−1 followed by two maintenance doses of 2.5 mg kg−1 at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l−1 for 72 h.Conclusions Phenobarbital, given as an i.v. loading dose, 15 mg kg−1, achieves maximum plasma concentrations of greater than 15 mg l−1 with good clinical effect and no significant adverse events in children with severe falciparum malaria. A maintenance dose of 2.5 mg kg−1 at 24 h and 48 h was predicted to be sufficient to maintain concentrations of 15–20 mg l−1 for 72 h, and may be a suitable regimen for treatment of convulsions in these children.

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Section: Discussionsupporting

confidence: 67%

Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

Kokwaro

Ogutu

Muchohi

et al. 2003

Brit J Clinical Pharma

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“…Nevertheless, in infants with a lower gestational age phénobarbital levels after loading decreased more rapidly than in neo nates with a greater gestational age, this may be due to a greater volume of distribution of the drug [11][12][13][14][15][16][17][18][19][20], to lower serum protein concentrations and a greater distribution to tissues [13,14], During intramuscular maintenance, the liver immaturity and the reduced renal clear ance became more evident: babies in group I showed significantly higher phénobarbital plasma levels than those in group II. The dif ference observed persisted during the whole therapeutic period, also because the enzyme autoinduction matures more slowly in pre term babies [25].…”

Section: Resultsmentioning

confidence: 99%

Phenobarbital for Treatment of Seizures in Preterm Infant: A New Administration Scheme

Carolis

Muzii²,

Romagnoli³

et al. 1990

Dev Pharmacol Ther

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The serum concentration of phenobarbital used as an anticonvulsant was monitored in 30 preterm babies. The therapeutic serum concentration was achieved with a loading dose of 20 mg/kg i.v., 10 min after administration. Thirty-six hours after loading, it was possible to maintain therapeutic serum levels with a daily intramuscular dose of 5 mg/kg, avoiding toxicity. A comparison of CSF and serum concentrations indicated that the drug passage to CSF is rapid and depends on a brain lesion. Serum monitoring of phenobarbital is important in preterm neonates under 30 weeks gestation and/or with severe pathological complications.

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“…In addition, comparing oral administration with the intramuscular route, there is a difference of about 60% in terms of bioavailability in newborns (Yukawa et al, 2011). Newborns present a late and incomplete oral absorption of PB when compared with intramuscular administration (Jalling, 1975). Furthermore, the narrow therapeutic margin of this anticonvulsant is one of the aggravating factors for the treatment of epileptic seizures, since the usual doses may lead plasma concentrations to toxic levels.…”

Section: Introductionmentioning

confidence: 99%

Phenobarbital loaded microemulsion: development, kinetic release and quality control

Figueiredo

Neves

Silva

et al. 2016

Braz. J. Pharm. Sci.

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This study aimed to obtain and characterize a microemulsion (ME) containing phenobarbital (PB). The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol ® , ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV λ = 242 nm. The kinetics of the in vitro release (Franz model) of the ME and the emulsion (EM) containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.Uniterms: Microemulsion/physicochemical characterization. Microemulsion/In vitro release. Phenobarbital/microemulsion system/evaluation. Nanotechnology.O objetivo deste trabalho foi obter e caracterizar uma microemulsão (ME) contendo fenobarbital (FEN). O FEN foi incorporado na proporção de 5% e 10% em um sistema microemulsionado composto por labrasol ® , etanol, miristato de isopropila e água purificada. Foi realizada a caracterização físico-química e avaliada a estabilidade preliminar da ME. Desenvolveu-se um método analítico por espectrofotometria em UV λ = 242 nm. Foi avaliada a cinética de liberação in vitro (em modelo de Franz) da ME e da emulsão (EM) contendo FEN. A incorporação do FEN em ME nas concentrações de 5 e 10% não alterou o pH e a resistência à centrifugação. Houve aumento do tamanho da partícula, redução da condutividade e alteração do índice de refração em relação à ME placebo. A ME manteve-se estável nos ensaios de estabilidade preliminar. O método analítico demonstrou ser específico, linear, preciso, exato e robusto. Na cinética de liberação in vitro, a ME obteve um perfil de liberação in vitro superior a EM contendo FEN. Desta forma, a ME obtida tem potencial para uma futura aplicação transdérmica, podendo compor um sistema de liberação de fármacos para tratamento da epilepsia.Uniterms: Microemulsão/caracterização físico-química. Microemulsão/cinética de liberação in vitro. Fenobarbital/sistema microemulsionado/avaliação. Nanotecnologia.

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Plasma Concentrations of Phenobarbital in the Treatment of Seizures in Newborns

Cited by 60 publications

References 10 publications

Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

Phenobarbital for Treatment of Seizures in Preterm Infant: A New Administration Scheme

Phenobarbital loaded microemulsion: development, kinetic release and quality control

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