Comparative pharmacokinetics of four cholinesterase inhibitors in rats.
Pharmacokinetics of a very short-acting, a short-acting and two long-acting cholinesterase (ChE) inhibitors, edrophonium, neostigmine, pyridostigmine and ambenonium, respectively, were compared to elucidate the major determinant of their pharmacokinetics. No dose-dependency in pharmacokinetic behavior was observed within the range of 2-10 mumol/kg for edrophonium, 0.5-2 mumol/kg for pyridostigmine, 0.1-0.5 mumol/kg for neostigmine and 0.3-3 mumol/kg for ambenonium, respectively. Neostigmine has the shortest elimination half-life, and edrophonium, pyridostigmine and ambenonium follow in that. Four ChE inhibitors have similar Vdss values within the range of 0.3-0.7 l/kg, which is similar to the muscle/plasma concentration ratio of these drugs. The liver or kidney to plasma concentration ratio of all ChE inhibitors at 20min after i.v. administration ranged from 5 to 15. Small distribution volumes estimated from the plasma concentration profiles may reflect the distribution to muscle and to the extracellular space of other organs/tissues, while the rapid disappearance of ChE inhibitors from plasma may reflect the concentrative uptake to the liver and kidney.
Yamamoto
K
K
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Sawada
Y
Y
Iga
T
T
D000549:Ambenonium Chloride / Q000493:pharmacokinetics; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D004491:Edrophonium / Q000493:pharmacokinetics; D006207:Half-Life; D008297:Male; D009388:Neostigmine / Q000493:pharmacokinetics; D011729:Pyridostigmine Bromide / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D000549:Ambenonium Chloride; D004491:Edrophonium; D011729:Pyridostigmine Bromide