Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring.
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.
Cazzola
E
E
Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi, Milano, Italy.
Lattuada
N
N
Zecca
L
L
Radice
D
D
Luzzana
M
M
Imbimbo
B P
BP
Auteri
A
A
Mosca
A
A
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
D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine; D002802:Cholinesterases