COMPARISON OF THE PHARMACOKINETICS OF E2020, A NEW COMPOUND FOR ALZHEIMERS-DISEASE, IN HEALTHY-YOUNG AND ELDERLY SUBJECTS

E2020, a central-acting cholinesterase inhibitor, is now under clinica l development as a potential therapeutic agent for senile dementia of Alzheimer type. In the current study, the authors compared the pharmac okinetics of this drug after single oral administration in 12 healthy young volunteers (20-27 years of age) and 6 elderly volunteers (65-82 years of age). The subjects received a single 2-mg oral dose of E2020 after a meal. Blood samples for determination of the drug level were c ollected over 168 hours after drug administration and were measured by specific high-pressure liquid chromatography methods with ultraviolet detection. E2020 was generally well tolerated by all subjects of both groups. The plasma elimination half-life of the beta-phase (t1/2beta) and time to maximum peak plasma concentration (tmax) were significant ly longer in the elderly than in the young: t1/2beta, 103.8 +/- 40.6 v ersus 59.7 +/- 16.1 hours; and tmax, 5.2 +/- 2.8 versus 3.4 +/- 1.5 ho urs, respectively. There were no statistically significant differences in maximum peak plasma concentration and area under the curve between the two groups. The mean (+/-standard deviation) oral clearance (Cl/F ) in the elderly (9.1 +/- 2.4 L/h) was similar to that in the young (1 0.6 +/- 2.7 L/h). The volume of distribution in the steady state (Vd(s s)/F) was significantly larger in the elderly than that in the young: 1217.2 +/- 223.2 versus 852.5 +/- 147.7 L, respectively. These results suggested that the drug was absorbed more slowly and distributed more widely and thoroughly, but that its clearance from the body is essent ially unaffected by age. It is concluded that a modification of the do se of E2020 in the elderly is unnecessary.