Age and phenytoin kinetics in adult epileptics

Michaelis-Menten parameters for rate of drug metabolism (Vmax) and serum concentration at which metabolism is half of Vmax (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, Vmax 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 less than 0.05). Linear regression analysis indicated a decline in Vmax with age (r = 0.518). Km values did not appear to be influenced by age; means ranged from 5.4 to 5.8 microgram/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 microgram/ml. First doses can be based on these data and maintenance doses arrived at based on clinical response.