Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

Abstract

Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

• Authors: M Šíma, P Pokorná, K Hronová, O Slanař
• Journal: Physiological research (Physiol Res) Vol. 64 Issue Suppl 4 Pg. S513-9 ( 2015) ISSN: 1802-9973 [Electronic] Czech Republic
• PMID: 26681081 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Anticonvulsants
• Vasoconstrictor Agents
• Phenobarbital

Topics

• Analgesics (administration & dosage, pharmacokinetics)
• Anticonvulsants (administration & dosage, pharmacokinetics)
• Drug Interactions (physiology)
• Drug Therapy, Combination
• Female
• Humans
• Hypoxia-Ischemia, Brain (diagnosis, drug therapy, metabolism)
• Infant, Newborn
• Male
• Phenobarbital (administration & dosage, pharmacokinetics)
• Prospective Studies
• Treatment Outcome
• Vasoconstrictor Agents (administration & dosage, pharmacokinetics)