• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jpnSubmit a ManuscriptEmail AlertsAbout JPNJournal of Psychiatry and Neuroscience
J Psychiatry Neurosci. Nov 1996; 21(5): 334–339.
PMCID: PMC1188798

Bioavailability and pharmacokinetic disposition of tacrine in elderly patients with Alzheimer's disease.

Abstract

The pharmacokinetic disposition of intravenous and oral doses of tacrine was determined in 5 elderly patients (aged 64 to 96 y) with the clinical diagnosis of Alzheimer's disease. The bioavailability of the oral formulation was low (9.9% to 36.4%), and the plasma half-life was not altered by route of drug delivery. These data indicate that tacrine elimination occurs by a 1st-order process. Plasma clearance of tacrine varied more than its half-life, which is consistent with a modulating effect of apparent volume of distribution (Vd). Our findings, together with other limited published studies, suggest that use of tacrine for the treatment of Alzheimer's disease (AD) will be confounded by the high interindividual variability in its kinetic disposition.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (803K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ahlin A, Adem A, Junthé T, Ohman G, Nybäck H. Pharmacokinetics of tetrahydroaminoacridine: relations to clinical and biochemical effects in Alzheimer patients. Int Clin Psychopharmacol. 1992 Spring;7(1):29–36. [PubMed]
  • Ahlin A, Hassan M, Junthé T, Nybäck H. Tacrine in Alzheimer's disease: pharmacokinetic and clinical comparison of oral and rectal administration. Int Clin Psychopharmacol. 1994 Winter;9(4):263–270. [PubMed]
  • Askmark H, Aquilonius SM, Gillberg PG, Hartvig P, Hilton-Brown P, Lindström B, Nilsson D, Stålberg E, Winkler T. Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis. Acta Neurol Scand. 1990 Oct;82(4):253–258. [PubMed]
  • Cutler NR, Sedman AJ, Prior P, Underwood BA, Selen A, Balogh L, Kinkel AW, Gracon SI, Gamzu ER. Steady-state pharmacokinetics of tacrine in patients with Alzheimer's disease. Psychopharmacol Bull. 1990;26(2):231–234. [PubMed]
  • Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976 Dec 25;2(8000):1403–1403. [PubMed]
  • Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI, Drachman DA, Schneider LS, Whitehouse PJ, Hoover TM, et al. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group. N Engl J Med. 1992 Oct 29;327(18):1253–1259. [PubMed]
  • Eagger SA, Levy R, Sahakian BJ. Tacrine in Alzheimer's disease. Lancet. 1991 Apr 27;337(8748):989–992. [PubMed]
  • Farlow M, Gracon SI, Hershey LA, Lewis KW, Sadowsky CH, Dolan-Ureno J. A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group. JAMA. 1992 Nov 11;268(18):2523–2529. [PubMed]
  • Forsyth DR, Ford JM, Truman CA, Roberts CJ, Wilcock GK. Determination of tacrine hydrochloride in human serum by chloroform extraction, reversed-phase high-performance liquid chromatography and fluorimetric detection. J Chromatogr. 1988 Dec 9;433:352–358. [PubMed]
  • Forsyth DR, Wilcock GK, Morgan RA, Truman CA, Ford JM, Roberts CJ. Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease. Clin Pharmacol Ther. 1989 Dec;46(6):634–641. [PubMed]
  • Hartvig P, Askmark H, Aquilonius SM, Wiklund L, Lindström B. Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine. Eur J Clin Pharmacol. 1990;38(3):259–263. [PubMed]
  • Hartvig P, Pettersson E, Wiklund L, Lindström B. Pharmacokinetics and effects of 9-amino-1,2,3,4-tetrahydroacridine in the immediate postoperative period in neurosurgical patients. J Clin Anesth. 1991 Mar-Apr;3(2):137–142. [PubMed]
  • Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group. JAMA. 1994 Apr 6;271(13):985–991. [PubMed]
  • Maayani S, Weinstein H, Ben-Zvi N, Cohen S, Sokolovsky M. Psychotomimetics as anticholinergic agents. I. 1-Cyclohexylpiperidine derivatives: anticholinesterase activity and antagonistic activity to acetylcholine. Biochem Pharmacol. 1974 Apr 15;23(8):1263–1281. [PubMed]
  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. [PubMed]
  • Park TH, Tachiki KH, Summers WK, Kling D, Fitten J, Perryman K, Spidell K, Kling AS. Isolation and the fluorometric, high-performance liquid chromatographic determination of tacrine. Anal Biochem. 1986 Dec;159(2):358–362. [PubMed]
  • Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982 Sep;139(9):1136–1139. [PubMed]
  • Sitar DS. Metabolism and pharmacokinetics of drugs in the aging population. Clin Biochem. 1993 Dec;26(6):437–438. [PubMed]
  • Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med. 1986 Nov 13;315(20):1241–1245. [PubMed]

Articles from Journal of Psychiatry & Neuroscience : JPN are provided here courtesy of Canadian Medical Association

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...