Single-dose and steady-state pharmacokinetics of sabeluzole in senile dementia of Alzheimer type patients
- 23 Downloads
The single- and repeated-dose pharmacokinetics of sabeluzole have been determined in six elderly patients with [senile] dementia of the Alzheimer type.
After a single oral dose of 10 mg sabeluzole, the peak plasma concentration was attained at 1 to 4 h; it averaged 42 ng·ml−1. On repeated dosing (10 mg b. d.), steady-state was virtually attained after 3 days of treatment. Steadystate mean trough and peak plasma concentrations fluctuated between 53 and 94 ng·ml−1. The mean terminal half-life after a single dose and at steady-state was of the order of 33 h.
Sabeluzole was well tolerated and at the end of treatment, no systematic changes in blood haematology, biochemistry or urinalysis were seen.
KeywordsSabeluzole, Alzheimer pharmacokinetics, single and repeated dosing, (senile) dementia, tolerability
- 1.Wauquier A, Clincke G, Ashton D, De Ryck M, Fransen J, Van Clemen G (1986) R 58 735: Anew antihypoxic drug with anticonvulsant properties and possible effects on cognitive functions. Drug Dev Res 8: 373–380Google Scholar
- 2.Clincke G, Sahgal A (1986) R 58 735, a novel antihypoxic drug improves memory in rats. Drug Dev Res 8: 381–385Google Scholar
- 3.Pauwels PJ, Leysen JE and Janssen PAJ (1990) Resistance of sabeluzole-treated rat brain neuronal cultures to neuronal damage. Neurosci Res Corn 6: 19–26Google Scholar
- 4.Geerts H, Nuydens R, Nuyens R, Cornelissen F, De Brabander M, Pauwels P, Janssen PAJ, Song YH and Mandelkow EM (1992) Sabeluzole, a memory enhancing molecule increases fast axonal transport in neuronal cell cultures. Exp Neurol 117: 36–43Google Scholar
- 5.Clincke GHC, Tritsmans L, Idzikowski C, Amery WK, Janssen PAJ (1988) The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers. Psychopharmacol 94: 52–57Google Scholar
- 6.Clincke GHC, Tritsmans L (1988) Sabeluzole (R 58 735) increases consistent retrieval during serial learning and relearning of nonsense syllables. Psychopharmacol 96: 309–310Google Scholar
- 7.Tritsmans L, Clincke G, Amery WK (1988) The effect of sabeluzole (R 58 735) on memory retrieval functions. Psychopharmacol 94:527–531Google Scholar
- 8.Tritsmans L, Clincke G, Devenijns F, Verhoolsel G, Amery WK (1988) Memory study with sabeluzole in a population with a mean age of 85 years: a pilot experiment. Current Ther Res 44: 966–974Google Scholar
- 9.McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) 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 34: 939–944Google Scholar
- 10.Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd ed, Dekker, New YorkGoogle Scholar
- 11.Van de Velde V, Van Peer A, Tritsmans L, Gasparini R, Woestenborghs R, Heykants J, Amery W (1986) Single and repeated dose pharmacokinetics of R 58 735 in healthy volunteers. Pharmaceutisch Weekblad (Scientific Edition) 8: 311Google Scholar
- 12.Van Peer A, Tritsmans L, Gasparini R, Woestenborghs R, Lorreyne W, Heykants J, Amery W (1986) Multiple dose pharmacokinetics of R 58 735 10 mg b. i. d. in healthy volunteers. Clinical Research Report R58735/3, Janssen Research Foundation, Beerse, BelgiumGoogle Scholar