Impact of drug‐drug interactions on phenobarbital pharmacokinetics in pediatric patients

Šíma, Martin; Slanař, Ondřej

doi:10.1111/epi.14704

Cited by 2 publications

(2 citation statements)

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“…Moffett et al reported a decrease in phenobarbital CL with concomitant use of midazolam and phenytoin, and an increase if pantoprazole was used [39]. However, this finding has been questioned [54,55]. Midazolam is a substrate of the CYP3A4 isoenzyme, which is not associated with phenobarbital metabolism [68].…”

Section: Discussionmentioning

confidence: 99%

“…Michaličková et al also did not observe any effect of diuretics and inotrope use on phenobarbital CL in critically-ill neonates undergoing ECMO [41]. Although Moffett et al concluded that midazolam, phenytoin, and pantoprazole significantly affected phenobarbital CL [39], this finding has been questioned as a chance finding only [54,55]. The cytochrome P450 2C19 genotype did not also affect phenobarbital pharmacokinetics in neonates and infants [47].…”

Section: Drug Interactions and Genetic Polymorphismsmentioning

confidence: 95%

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What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?

2021

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Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.

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