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Single‐Dose Pharmacokinetics, Safety, and Tolerance of Linopirdine (DuP 996) in Healthy Young Adults and Elderly Volunteers
Author(s) -
Pieniaszek Henry J.,
Fiske William D.,
Saxton Timothy D.,
Kim Yong S.,
Garner Dennis M.,
Xilinas Mikis,
Martz Robert
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04741.x
Subject(s) - pharmacokinetics , medicine , placebo , adverse effect , urine , pharmacology , anesthesia , pathology , alternative medicine
The pharmacokinetics, safety, and tolerance of linopirdine ([3,3‐bis(4‐pyridinylmethyl)‐1‐phenylindolin‐2‐one];DuP 996) a potential therapeutic agent for Alzheimer's disease, were assessed in double‐blind, placebo‐controlled, randomized studies in which single oral doses were given to 64 healthy young or elderly males. Young subjects received escalating 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 after liquid extraction by a specific HPLC method using UV detection. In both groups, linopirdine disposition was characterized by rapid absorption (mean T max , <1 hr) and elimination (mean t 1/2 , 0.4–3.2 hr). Urinary excretion of unchanged drug was negligible. The pharmacokinetic parameters showed large inter‐ and intrasubject variability. Linopirdine was well‐tolerated in both young and elderly volunteers. The most frequently reported adverse event was headache. The subjects who received linopirdine did not experience clinically important changes in vital signs, electrocardiograms (ECGs), electroencephalograms (EEGs), or clinical laboratory evaluations.