title: Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects.
abstract: 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 (t1/2 alpha = 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.
authors.affiliation: Istituto di Patologia Speciale Medica, Università di Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Auteri
authors.forename: A
authors.initials: A
authors.lastname: Mosca
authors.forename: N
authors.initials: N
authors.lastname: Lattuada
authors.forename: M
authors.initials: M
authors.lastname: Luzzana
authors.forename: L
authors.initials: L
authors.lastname: Zecca
authors.forename: D
authors.initials: D
authors.lastname: Radice
authors.forename: B P
authors.initials: BP
authors.lastname: Imbimbo
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine; D002802:Cholinesterases