title: Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring.
abstract: Eptastigmine (MF 201) is a new physostigmine derivative with potent inhibitory activity on cholinesterases. Here we present a new potentiometric cholinesterase activity assay suitable for MF 201 monitoring. The analysis is performed on a differential pH system and has the following characteristics: (a) within-run precision: C.V. 2.0% (plasma cholinesterase), 1.8% (red cell cholinesterase); (b) between-run precision: C.V. 4.0% (plasma cholinesterase); (c) linearity: 1-10 kU/l (plasma cholinesterase), 6-70 U/g Hb (red cell cholinesterase); (d) comparison with a reference method (x, HITACHI 737 Boerhinger Mannheim, Italy): y = 0.785x - 0.07; n = 37; r = 0.998. The assay has been applied to the determination of plasma and red cell cholinesterase activity in volunteers over 60 years of age treated with a single oral dose of 30 mg eptastigmine. We found that red cell cholinesterase is selectively inhibited after MF 201 administration with the following kinetics (time, % of inhibition, mean +/- S.E., n = 6): 0 h, 0; 1 h, 17 +/- 4.6; 2 h, 24 +/- 4; 4 h, 23 +/- 4.4; 12 h, 14 +/- 3. Eptastigmine plasma levels were also determined by a HPLC method: maximum concentration was found one hour after drug administration.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi, Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cazzola
authors.forename: N
authors.initials: N
authors.lastname: Lattuada
authors.forename: L
authors.initials: L
authors.lastname: Zecca
authors.forename: D
authors.initials: D
authors.lastname: Radice
authors.forename: M
authors.initials: M
authors.lastname: Luzzana
authors.forename: B P
authors.initials: BP
authors.lastname: Imbimbo
authors.forename: A
authors.initials: A
authors.lastname: Auteri
authors.forename: A
authors.initials: A
authors.lastname: Mosca
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*; D016903:Drug Monitoring / Q000379:methods; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D011199:Potentiometry / Q000379:methods
chemical_list: D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine; D002802:Cholinesterases