Factors affecting antiepileptic drug pharmacokinetics in community-dwelling elderly.

Because aging is associated with changes in physiological processes, it is widely believed that antiepileptic drug pharmacodynamics and pharmacokinetics in elderly patients differ from those in younger adults. In order to better characterize these differences, this chapter reports on preliminary results from an investigation of the effect of age on steady-state phenytoin (PHT) and carbamazepine (CBZ) pharmacokinetics. Parenteral formulations of stable-labeled PHT, fosphenytoin (FOS), and CBZ were administered to elderly (> or =65 years of age) and adult (18-64 years of age) patients on maintenance regimens of PHT or CBZ; a labeled 100-mg dose was infused over 10 min, then the remainder of the patient's AED dose was administered as unlabeled drug. Blood samples were collected just before administration of the labeled drug and for up to 192 h afterward. Samples were then assayed for the concentrations of labeled and unlabeled drug. Preliminary results from 60 patients on PHT therapy (41 elderly, mean age 76 years; 19 younger adults, mean age 41 years) indicate that PHT bioavailability did not differ between the two age groups; however, absorption and elimination half-lives were more variable in the elderly patients. The elimination half-life for the entire patient population was approximately twofold longer than the value reported in the product labeling (40-50 h vs 22 h). Preliminary results from 67 patients on CBZ therapy (14 elderly, mean age 70 years; 53 younger adults, mean age 41 years) showed no apparent difference between elderly and adult patients in any parameter; however, the mean CBZ elimination half-life for the combined groups (21 h) was longer than previous estimates. These results indicate that the effect of age on CBZ and PHT absorption may result in greater variability in plasma concentrations in elderly patients, whereas the effect on half-life is modest.