Phenobarbital population pharmacokinetics across the pediatric age spectrum

Abstract

Phenobarbital dosing of 30 mg kg dose ,iv, followed by 4 mg kg d had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions.

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

“…To the Editors: We have read with great interest the article "Phenobarbital population pharmacokinetics across the pediatric age spectrum" by Moffett et al 1 The authors concluded that midazolam, phenytoin, and pantoprazole significantly affected phenobarbital clearance and that these drug-drug interactions should be incorporated into dosing decisions. We are of the opinion that such a conclusion and dosing adjustment recommendation are not supported by scientifically sound evidence in its totality.…”

A retrospective comparison of phenobarbital and levetiracetam for the treatment of seizures following cardiac surgery in neonates

“…It is metabolized by the liver via cytochrome P450 and primarily excreted by the kidneys 12 . PHB pharmacokinetics is notable for maturation‐related changes in clearance in the first months of life, auto‐inducible clearance with use, and numerous drug interactions 12,13 . Prior studies in neonates, including randomized controlled trials, have reported PHB efficacy of 40%‐50% for neonatal seizures, although success rates as high as 72% have been reported 14–17 .…”

Phenobarbital Pharmacokinetics and Optimal Dosing

“…Also, the drug–drug interactions of midazolam, phenytoin, and pantoprazole significantly affected phenobarbital concentrations. [1]…”

“…The bioavailability of Phenobarbital has been documented at ~90% in adults and shown to be much less in neonatal populations [1]. It is hypothesized that growth-related changes in organ function and maturation of enzyme systems used to metabolize phenobarbital (2C19 subunit of the CYP Enzyme, matures significantly in first 6 months of life) play a factor.…”

“…The study also reconfirmed that pantoprazole increased phenobarbital clearance and phenytoin decreased its clearance. Unique to this study was a new finding that midazolam decreased phenobarbital clearance [1]. The study made no comment on morphine or opioid receptor based medications and their effect on phenobarbital.…”