Pyridostigmine Kinetics with and without Renal Function

Abstract

Pyridostigmine kinetics were examined under conditions of clinical use as an antagonist of nondepolarizing neuromuscular blockade in anesthetized patients with and without renal function. Pyridostigmine serum levels were assayed by gas-liquid chromatography, and data were fitted to a 2-compartment kinetic model. Pyridostigmine kinetics following renal transplantation (n = 5) were not different from those in patients with normal renal function. Renal function (n = 5) elimination half-life increased from 112 -± 12 min (S ± SD) to 379 -± 162 mm, and serum clearance decreased from 9 ± 2 ml/kg/min to 2 ± 0.6 ml/kg/min in anephric patients (n = 4). We conclude that renal function accounts for 75% of pyridostigmine clearance.Impaired renal function decreases plasma clearance and prolongs duration of action of some nondepolarizing muscle relaxants, which may account for problems of prolonged neuromuscular blockade in patients with renal failure.12-13' 15' 19 We recently found that renal failure also decreased plasma clearance and prolonged elimination half-life of neostigmine, an antagonist of nondepolarizing neuromuscular blockade.4 We wondered whether this also applied to another common antagonist, pyridostigmine, which has a slower onset and longer duration of antagonist activity in anesthetized patients than neostigmine.16 Therefore pyridostigmine kinetics were examined in patients with and without renal function and after kidney transplantation. We also sought to determine

Anticholinesterase-resistant neuromuscular blockade in sheep given amino-steroid muscle relaxants

“…It was believed previously that 'recurarisation' in people was likely in renal failure when relaxant action outlasted anticholinesterase. This is unlikely because edrophonium, neostigmine and pyridostigmine rely on kidney function for elimination and in renal failure, antagonist clearance is reduced more than neuromuscular blocking agent; neostigmine clearance is reduced 2.5 times (Cronnelly et al, 1979), pyridostigmine, 4 times (Cronnelly et al, 1980) and edrophonium, 4 times .…”

Succinylcholine resistance

“…The half-life of neostigmine is 77 min 27 and for pyridostigmine it is 113 min. 28 A blood sample for BChE activity should therefore be drawn the next day.…”

Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure

“…Once it enters the bloodstream, PB is widely distributed throughout the body, with reported volumes of distribution of 1.0 (Breyer-Pfaff et al 1985) or 1.1 (Cronnelly et al 1980) to 1.76 L/kg (Aquilonius and Hartvig 1986). The most recent study to address this issue postulated a two-compartment model with a volume of distribution of 2.09 L/kg for the central compartment and 4240 L for the peripheral compartment (Marino et al 1998).…”

“…Although glucuronidation by the liver is not the major pathway by which PB leaves the body, it has been suggested that liver disease may be at least a relative contraindication (Institute of Medicine 1996). In uremic patients, there is no change in the volume of distribution of PB (Benet et al 1996) but a decrease in plasma clearance (Cronnelly et al 1980) and an increase in the elimination half-life (Benet et al 1996), and the dose of PB should be decreased in elderly patients and in patients with significant renal disease (Arky 1998).…”