Phenytoin Michaelis-Menten pharmacokinetics in Caucasian paediatric patients. 1983

L A Bauer, and R A Blouin

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 135 epileptic paediatric patients receiving phenytoin as their only anticonvulsant therapy. Mean Vmax and Km values were 13.95 mg/kg/day and 6.59 micrograms/ml for 0.5 to 3-year-old patients, 10.93 mg/kg/day and 6.82 micrograms/ml for the 4 to 6 year age group, 10.05 mg/kg/day and 6.51 micrograms/ml for the 7 to 9-year-olds, and 8.25 mg/kg/day and 5.69 micrograms/ml for the 10 to 16 year group. Using analysis of variance, the Vmax values were significantly different (p less than 0.01) but the Km values were not. Linear regression analysis of Vmax versus age revealed a significant decline in Vmax with age (r = -0.554; p less than 0.001). A plot of Km versus age showed a poor correlation (r = -0.170) and a large amount of variability. Based on this data, the youngest age group would require on average 62% more phenytoin/kg/day than the oldest age group in order to maintain a steady-state phenytoin concentration of 15 micrograms/ml. Because of these age-related pharmacokinetic differences, phenytoin dosages may require adjustment as paediatric patients become older.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging

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