title: Pharmacokinetics and pharmacodynamics
text: Pharmacokinetics and pharmacodynamics:
  In infants with seizures, phenobarbital 15−20 mg loading dose with additional 5−10 mg/kg doses to maximal plasma concentration of 40 mg/L (172 micromol/L) resulted in a plateau of the response rate. Plasma concentrations >50 mg/L (215 micromol/L) were associated with sedation and feeding difficulty.[9]
  The clearance of phenobarbital increases with birth weight and postnatal age, but is reduced at a concentration >50 mg/L (215 micromol/L). [10] Bioavailability is 50% after oral administration. Simulations recommend a loading dose 20 mg/kg and maintenance 2.5 − 5 mg/kg/day for intravenous administration and; loading dose 40 mg/kg and maintenance 5 − 11 mg/kg/day for oral administration to meet a target phenobarbital concentration between 15 and 30 mg/L (64.5 and 129.1 micromol/L) [11]. (LOE IV GOR C)
  The clearance may also be reduced in infants with perinatal asphyxia undergoing therapeutic hypothermia.[12-14] In term infants treated with hypothermia, an initial phenobarbital loading dose of 20 mg/kg with an additional 10−20 mg/kg if needed is recommended. [14] (LOE IV GOR C)
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