title: 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.affiliation: Department of Pharmacology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. sima.mart@seznam.cz.
authors.forename: M
authors.initials: M
authors.lastname: Šíma
authors.forename: P
authors.initials: P
authors.lastname: Pokorná
authors.forename: K
authors.initials: K
authors.lastname: Hronová
authors.forename: O
authors.initials: O
authors.lastname: Slanař
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D014662:Vasoconstrictor Agents; D010634:Phenobarbital