Lk. Unni et al., ORAL-ADMINISTRATION OF HEPTYLPHYSOSTIGMINE IN HEALTHY-VOLUNTEERS - A PRELIMINARY-STUDY, Methods and findings in experimental and clinical pharmacology, 16(5), 1994, pp. 373-376
Heptylphysostigmine (HP) is a reversible cholinesterase (ChE) inhibito
r with greater lipophilicity and longer inhibitory action than the par
ent compound physostigmine (Phy). Single (0.1-0.6 mg/kg) and multiple
5-day (0.1-0.3 mg/kg) doses of HP were administered to 21 young normal
volunteers. The relationship between logarithmic dose (mg/kg) and pea
k inhibition of red blood cell (RBC) ChE was linear with dose. In one
subject given 0.6 mg/kg of HP concentration in plasma was 0.68 ng/ml a
t 2 h and gradually declined to below the detection limit by 4 h. Peak
plasma and RBC ChE inhibitions of 31.2% and 55.8% were achieved at 2
h for both with a 0.6 mg/kg dose. Chronic studies did not result in an
y accumulation of ChE inhibition up to 0.2 mg/kg b.i.d., whereas at 0.
3 mg/kg b.i.d. 10-15% RBC ChE inhibition was maintained. Higher levels
of ChE inhibition can be achieved with HP than with its parent compou
nd, Phy, Red blood cell ChE inhibition recovered more slowly than plas
ma even though the maximum inhibition was similar for both enzymes.