Aging alters the pharmacokinetics of pyridostigmine

The duration of the antagonism to neuromuscular blockade produced by pyridostigmine is prolonged in elderly patients, and a pharmacokinetic explanation was sought. Ten elderly (71-85 yr) and 10 younger (21-51 yr) patients were anesthetized with thiopental, nitrous oxide, and isoflurane and paralyzed with a combination of d-tubocurarine and pancuronium. When twitch height returned to 5% of baseline, pyridostigmine 0.25 mg/kg was administered and blood samples were collected intermittently for 6 h. Pyridostigmine plasma concentrations were determined by radioimmunoassay and after an hour were always greater in the elderly than in the younger patients. In both groups, plasma pyridostigmine decrement curves were best described by triexponential equations. Pharmacokinetic analysis revealed that plasma clearance in the elderly group was significantly decreased compared to that in the younger group (6.7 ± 2.2 vs 9.5 ± 2.7 mL · kg^-1 · min^-1, P < 0.05). Elimination half-lives and volumes of distribution were not significantly different between groups. We conclude that a possible explanation for the prolonged duration of action of pyridostigmine in the elderly is its slow plasma clearance.