title: Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease.
abstract: The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose. The serum half-life was 1.59 +/- 0.15 hours (mean +/- SEM) after the 25 mg dose, 2.14 +/- 0.24 hours after the 50 mg dose, and 2.91 +/- 0.39 hours after continuous treatment. After intravenous administration, clearance was above 600 ml/min in both patients, and oral bioavailability was calculated at below 5%. Urine recovery was less than 3% of the dose. The low bioavailability of tacrine hydrochloride is partly explained by presystemic metabolism.
authors.affiliation: University Department of Medicine, Bristol Royal Infirmary, England.
authors.forename: D R
authors.initials: DR
authors.lastname: Forsyth
authors.forename: G K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: R A
authors.initials: RA
authors.lastname: Morgan
authors.forename: C A
authors.initials: CA
authors.lastname: Truman
authors.forename: J M
authors.initials: JM
authors.lastname: Ford
authors.forename: C J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000609:Aminoacridines / Q000493:pharmacokinetics*; D001682:Biological Availability; D001919:Bradycardia / Q000139:chemically induced; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D016018:Least-Squares Analysis; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013619:Tacrine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000609:Aminoacridines; D013619:Tacrine