TY - JOUR
T1 - Impairment of lidocaine clearance in elderly male subjects
AU - Abernethy, Darrell R.
AU - Greenblatt, David J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1983
Y1 - 1983
N2 - 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 (t1/2) 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 t1/2 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 t1/2 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%.
AB - 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 (t1/2) 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 t1/2 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 t1/2 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%.
KW - Drug clearance
KW - Geriatrics
KW - Half-life
KW - Lidocaine
KW - Pharmacokinetics
KW - Ventricular arrhythmia
UR - http://www.scopus.com/inward/record.url?scp=0021032982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021032982&partnerID=8YFLogxK
U2 - 10.1097/00005344-198311000-00027
DO - 10.1097/00005344-198311000-00027
M3 - Article
C2 - 6196560
AN - SCOPUS:0021032982
VL - 5
SP - 1093
EP - 1096
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 6
ER -