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Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine 228 38 38 3 3 P. Hartvig H. Askmark S. M. Aquilonius L. Wiklund B. Lindström Hospital Pharmacy University hospital Uppsala Sweden Department of Neurology University hospital Uppsala Sweden Department of Anesthesiology University hospital Uppsala Sweden Department of Drugs National Board of Health and Welfare Uppsala Sweden Summary The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l·h −1 . Volume of distribution, V α varied 100–680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6–36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Clinical Pharmacology Springer Journals

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine

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References (19)

Publisher
Springer Journals
Copyright
Copyright © 1990 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology
ISSN
0031-6970
eISSN
1432-1041
DOI
10.1007/BF00315027
Publisher site
See Article on Publisher Site

Abstract

228 38 38 3 3 P. Hartvig H. Askmark S. M. Aquilonius L. Wiklund B. Lindström Hospital Pharmacy University hospital Uppsala Sweden Department of Neurology University hospital Uppsala Sweden Department of Anesthesiology University hospital Uppsala Sweden Department of Drugs National Board of Health and Welfare Uppsala Sweden Summary The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l·h −1 . Volume of distribution, V α varied 100–680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6–36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.

Journal

European Journal of Clinical Pharmacology – Springer Journals

Published: Mar 1, 1990

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