SINGLE-DOSE PHARMACOKINETICS, SAFETY, AND TOLERANCE OF LINOPIRDINE (DUP-996) IN HEALTHY-YOUNG ADULTS AND ELDERLY VOLUNTEERS

The pharmacokinetics, safety, and tolerance of linopirdine 3,3-bis(4-p yridinylmethyl)-1-phenylindolin-2-one]; DuP 996) a potential therapeut ic agent for Alzheimer's disease, were assessed in double-blind, place bo-controlled, randomized studies in which single oral doses were give n to 64 healthy young or elderly males. Young subjects received escala ting doses of 0.5 to 55 mg, whereas elderly subjects were given doses of 20 to 45 mg. Linopirdine plasma and urine samples were quantified a fter liquid extraction by a specific HPLC method using UV detection. I n both groups, linopirdine disposition was characterized by rapid abso rption (mean T-max, <1 hr) and elimination (mean t(1/2), 0.4-3.2 hr). Urinary excretion of unchanged drug was negligible. The pharmacokineti c parameters showed large inter- and intrasubject variability. Linopir dine was well-tolerated in both young and elderly volunteers. The most frequently reported adverse event was headache. The subjects who rece ived linopirdine did not experience clinically important changes in vi tal signs, electrocardiograms (ECGs), electroencephalograms (EEGs), or clinical laboratory evaluations.