AGING ALTERS THE PHARMACOKINETICS OF PYRIDOSTIGMINE

The duration of the antagonism to neuromuscular blockade produced by p yridostigmine is prolonged in elderly patients, and a pharmacokinetic explanation was sought. Ten elderly (71-85 yr) and 10 younger (21-51 y r) patients were anesthetized with thiopental, nitrous oxide, and isof lurane and paralyzed with a combination of d-tubocurarine and pancuron ium. When twitch height returned to 5% of baseline, pyridostigmine 0.2 5 mg/kg was administered and blood samples were collected intermittent ly for 6 h. Pyridostigmine plasma concentrations were determined by ra dioimmunoassay and after an hour were always greater in the elderly th an in the younger patients. In both groups, plasma pyridostigmine decr ement curves were best described by triexponential equations. Pharmaco kinetic analysis revealed that plasma clearance in the elderly group w as 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 ha lf-lives and volumes of distribution were not significantly different between groups. We conclude that a possible explanation for the prolon ged duration of action of pyridostigmine in the elderly is its slow pl asma clearance.