Impairment of lidocaine clearance in elderly male subjects

Six elderly male (65-75 years), seven elderly female (64-88 years), 15 young male (22-38 years), and nine young female (25-37 years) volunteers, all of normal body weight and clinically without cardiac or renal dysfunction, received a single 25-mg intravenous dose of lidocaine. Plasma concentrations of lidocaine were determined from blood samples drawn during 8 h following the lidocaine dose. Elimination half-life (t_1/2) was markedly prolonged in elderly male subjects as compared with that in young male subjects (mean ± SE: 2.70 ± 0.21 versus 1.66 ± 0.09 h; p < 0.001). No difference in t_1/2 was noted among female subjects (2.27 ± 0.21 versus 2.07 ± 0.07 h). Volume of distribution was greater in women than in men but was not influenced by age. Instead, prolongation in t_1/2 in elderly men was the result of a highly significant decrease in total metabolic clearance (12.9 ± 2.0 versus 19.8 ± 1.5 ml/min/kg; p < 0.05). No significant change in total metabolic clearance of lidocaine was noted between elderly and young women (18.3 ± 2.0 versus 21.1 ± 1.6 ml/min/kg). The findings suggest that in the elderly male patient without evidence of congestive heart failure or other coexisting chronic disease, the initial loading dose of lidocaine should be the same as for a young patient. However, to achieve comparable plasma concentrations and therapeutic effect during continuous infusion therapy, the elderly male patient should have the continuous infusion rate decreased by an average of at least 35%.