TY - CHAP
T1 - Factors affecting Antiepileptic Drug Pharmacokinetics in Community-Dwelling Elderly
AU - Cloyd, James C.
AU - Marino, Susan
AU - Birnbaum, Angela K.
PY - 2007
Y1 - 2007
N2 - 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 (≥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.
AB - 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 (≥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.
UR - http://www.scopus.com/inward/record.url?scp=34047239775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047239775&partnerID=8YFLogxK
U2 - 10.1016/S0074-7742(06)81012-3
DO - 10.1016/S0074-7742(06)81012-3
M3 - Chapter
C2 - 17433925
AN - SCOPUS:34047239775
SN - 0123740185
SN - 9780123740182
T3 - International Review of Neurobiology
SP - 201
EP - 210
BT - The Neurobiology of Epilepsy and Aging
A2 - Ramsay, Eugene
A2 - Cloyd, James
A2 - Kelly, Kevin
A2 - Leppik, Ilo
A2 - Perucca, Emilio
ER -