Premium
Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease
Author(s) -
Forsyth Duncan R,
Wilcock Gordon K,
Morgan Robert A,
Truman Carol A,
Ford Julia M,
Roberts Clive J C
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.199
Subject(s) - tacrine , pharmacokinetics , pharmacology , alzheimer's disease , medicine , disease , chemistry , biochemistry , acetylcholinesterase , enzyme
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. Clinical Pharmacology and Therapeutics (1989) 46 , 634–641; doi: 10.1038/clpt.1989.199