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POPULATION PHARMACOKINETICS OF PHENYTOIN FROM ROUTINE CLINICAL DATA IN JAPAN
Author(s) -
Yukawa E.,
Higuchi S.,
Aoyama T.
Publication year - 1989
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.1365-2710.1989.tb00224.x
Subject(s) - pharmacokinetics , phenytoin , population pharmacokinetics , medicine , population , pharmacology , epilepsy , environmental health , psychiatry
Summary Routine clinical pharmacokinetic data collected from out‐patients who received phenytoin were analysed to estimate population pharmacokinetic parameters. There were 505 steady‐state phenytoin concentrations and associated dosage rates (mg/day) from 220 out‐patients. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The influence of weight on the maximum elimination rate ( V m ) and age on the Michaelis‐Menten constant ( K m ) or the influence of dosage form on the bioavailability ( F ) of phenytoin were investigated. The V m and K m of a 60‐kg adult out‐patient were estimated to be 369 mg/day and 3·67 mg/l, respectively. The parameter of a power function of weight was estimated to adjust V m for body size. The best function adjusts V m in proportion to weight to the 0–55 power. The K m for patients less than 15 years old was 16% less than that for adults. When the F of phenytoin is assumed to be 100% in the patients prescribed a tablet, the F value in the patients prescribed a powder was 89·5%.