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Age and phenytoin kinetics in adult epileptics
Author(s) -
Bauer Larry A,
Blouin Robert A
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.37
Subject(s) - phenytoin , microgram , bilirubin , metabolism , anticonvulsant , medicine , age groups , albumin , endocrinology , epilepsy , chemistry , biochemistry , demography , psychiatry , sociology , in vitro
Michaelis‐Menten parameters for rate of drug metabolism (V max ) and the serum concentration at which metabolism is half of V max (Km) were determined in 92 adult epileptic patients taking phenytoin who were 21 to 78 yr old. The patients received no known inhibitors or inducers of phenytoin metabolism. Results of physical examinations and tests of liver function and total bilirubin and albumin concentration were normal. Divided into age groups, V max values were 7.5 ± 2.2, 6.6 ± 1.8, and 6.0 ± 1.9 mg/kg/day for the 20‐ to 39‐, 40‐ to 59‐, and 60‐ to 79‐yr‐old subjects, respectively. Values for those in the 60‐ to 79‐yr‐old group were substantially less than those for the youngest subjects (20‐ to 39‐yr‐olds; P < 0.05). Linear regression analysis indicated a decline in V max with age (r = −0.518). Km values did not appear to be influenced by age; means ranged from 5.4 to 5.8 µg/ml. As a result of these changes, the 60‐ to 79‐yr‐old group would require, on the average, 21% less phenytoin per day than the 20‐ to 39‐year‐olds to maintain a steady‐state concentration of 15 µg/ml. First doses can be based on these data and maintenance doses arrived at based on clinical response. Clinical Pharmacology and Therapeutics (1982) 31, 301–304; doi: 10.1038/clpt.1982.37