Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns
Language English Country Czech Republic Media print
Document type Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
PubMed
26681081
DOI
10.33549/physiolres.933213
PII: 933213
Knihovny.cz E-resources
- MeSH
- Analgesics administration & dosage pharmacokinetics MeSH
- Anticonvulsants administration & dosage pharmacokinetics MeSH
- Phenobarbital administration & dosage pharmacokinetics MeSH
- Drug Therapy, Combination MeSH
- Drug Interactions physiology MeSH
- Humans MeSH
- Hypoxia-Ischemia, Brain diagnosis drug therapy metabolism MeSH
- Infant, Newborn MeSH
- Prospective Studies MeSH
- Vasoconstrictor Agents administration & dosage pharmacokinetics MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Analgesics MeSH
- Anticonvulsants MeSH
- Phenobarbital MeSH
- Vasoconstrictor Agents MeSH
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.
References provided by Crossref.org
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