Summary
Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63–84 years of age) given 30 mg eptastigmine as a single oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after eptastigmine administration for measurement of cholinesterase inhibition in plasma and red blood cells and the plasma drug concentrations.
The maximum plasma cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood cells. The peak plasma concentration of eptastigmine of 0.86 ng·ml−1 was reached after 1.4 h. Following absorption the drug was rapidly distributed into tissues (t1/2α = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug was well tolerated in all but one subject, who showed bradycardia with hypertension and nausea for about 2 h after the dose.
The results indicate that oral administration of eptastigmine to elderly subjects produces long lasting inhibition of cholinesterase activity in plasma and in red blood cells.
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References
Brufani M, Marta M, Pomponi M (1986) Anticholinesterase activity of a new carbamate, heptylphysostigmine, in view of its use in patients with Alzheimer-type dementia. Eur J Biochem 157: 115–120
Brufani M, Castellano C, Marta M, Oliverio A, Pagella PG, Pavone F, Pomponi M, Rugarli PL (1987) A long-lasting cholinesterase inhibitor affecting neural and behavioral processes. Pharmacol Biochem Behav 26: 625–629
Marta M, Castellano C, Oliverio A, Pavone F, Pagella PG, Brufani M, Pomponi M (1988) New analogs of physostigmine: alternative drugs for Alzheimer's disease? Life Sci 43: 1921–1928
Davis KL, Mohs RC (1982) Enhancement of memory processes in Alzheimer's disease with multiple dose intravenous physostigmine. Am J Psychiat 139: 1421–1424
Schwartz AS, Kohlstaedt EV (1986) Physostigmine effects in Alzheimer's diseases: Relationship to dementia severity. Life Sci 38: 1021–1028
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia of the Alzheimer type. N Engl J Med 315: 1241–1245
Perry EK (1986) The cholinergic hypothesis-ten years on. Br Med Bull 42: 63–69
De Sarno P, Pomponi M, Giacobini E, Trang XC, Williams E (1989) The effect of heptyl-physostigmine, a new cholinesterase inhibitor, on the central cholinergic system of the rat. Neurochem Res 14: 971–977
Dawson GR, Bentley G, Draper F, Rycroft W, Iversen SD, Pagella PG (1991) The behavioural effects of heptyl-physostigmine, a new cholinesterase inhibitor, in tests of long-term and working memory in rodents. Pharmacol Biochem Behav 39: 865–871
Rupniak NMJ, Tye SJ, Brazell C, Heald A, Iversen SD, Pagella PG (1992) Reversal of cognitive impairment by heptylphysostigmine, a long lasting cholinesterase inhibitor, in primates. J Neurol Sci 107: 246–249
Unni LK, Hutt V, Imbimbo BP, Becker RE (1991) Kinetics of cholinesterase inhibition of eptastigmine in man. Eur J Clin Pharmacol 41: 83–84
Goldberg MR, Barchowsky A, McCrea J, Ben-Maimon C, Capra N, Fitzpatrick V, Bjornsson TD (1991) Heptylphysostigmine (L-693, 487): safety and cholinesterase inhibition in a placebo-controlled rising-dose healthy volunteer study (abstract). 2nd International Springfield Symposium on Alzheimer Therapy, Spring-field
Cazzola E, Lattuada N, Zecca L, Radice D, Luzzana M, Imbimbo BP, Auteri A, Mosca A (1993) Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring. Chem Biol Interact 87: 265–268
Barenghi L, Ceriotti F, Luzzana M, Ripamonti M, Mosca A, Bonini PA (1986) Measurement of erythrocyte acetylcholinesterase and plasma cholinesterase activity by a differential pH technique. Ann Clin Biochem 23: 538–545
Heinzel G (1982) Salient points of various programs: TOPFIT. In: Bozler G, van Rossum JM (eds) Pharmacokinetics during drug development: data analysis and evaluation techniques. Fischer, Stuttgart
Becker RE, Giacobini E (1988) Mechanisms of cholinesterase inhibition in senile dementia of the Alzheimer type: clinical, pharacological and therapeutic aspects. Drug Develop Res 12: 163–195
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Auteri, A., Mosca, A., Lattuada, N. et al. Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects. Eur J Clin Pharmacol 45, 373–376 (1993). https://doi.org/10.1007/BF00265958
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DOI: https://doi.org/10.1007/BF00265958