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Population pharmacokinetic investigation of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants
Author(s) -
Yukawa E.,
Suematsu F.,
Yukawa M.,
Minemoto M.
Publication year - 2005
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2005.00619.x
Subject(s) - pharmacokinetics , suppository , phenobarbital , medicine , gestational age , population , anesthesia , pediatrics , pregnancy , pharmacology , environmental health , biology , genetics
Summary The population pharmacokinetics of phenobarbital was evaluated using 69 serum concentration measurements obtained from the routine phenobarbital monitoring of 35 neonates and infants. The data were analysed using the nonlinear mixed effects model. A one‐compartment open pharmacokinetic model with first‐order elimination was used. Covariates screened were current bodyweight (TBW), gestational age, postnatal age (PNA), postconceptional age and gender. The final pharmacokinetic parameters were CL/ F (mL/h) = 3·41·TBW (kg) + 1·64. PNA (weeks), V d / F (L) = 1·09 TBW. (kg), and F = 0·406 for oral administration and F = 1 for suppository. Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target phenobarbital concentrations, thus enabling the clinician to achieve the desired therapeutic effect in neonates and infants.