(14)C-lidocaine disposition in serum and tissues of normal and liver diseased rats.
OBJECTIVE
This study was designed to investigate the disposition of (14)C-lidocaine in serum and tissues in rats with liver dysfunction.


METHODS
Eighteen male rats were randomly divided into 2 groups. Group A was considered as control while group B underwent liver damage by administrating CCl(4) 0.4 mg/kg twice a week for 6 weeks. Both groups received 5 doses of 2.5 mg/kg lidocaine mixture (labeled (14)C-lidocaine and nonlabeled). The rats were killed 2 hours after the last dose. Total lidocaine levels ((14)C-lidocaine and (14)C-lidocaine metabolite concentrations) as well as the percent of total lidocaine-bound fractions in tissues were measured.


RESULTS
(14)C-lidocaine concentrations were significantly increased in the serum (9.4+/-0.4 microg/mL), heart (7.8+/-2 microg/gL), and mandible (0.97+/-0.01 microg/g) in diseased rats as compared with normal rats (serum, 5.3+/-1.7 microg/mL; heart, 4.2+/-0.9 microg/g; mandible, 0.68+/-0.02 microg/g, respectively). (14)C-lidocaine bound fractions in the mandible and heart did not show any significant differences between the 2 groups. Instead, (14)C-lidocaine bound fractions in serum were significantly reduced in diseased animals as opposed to normal ones.


CONCLUSIONS
We concluded that liver dysfunction can modify (14)C-lidocaine concentrations in the serum and tissues without altering the lidocaine binding properties in the mandible and heart.
Saranteas
Theodosios
T
Department of Pharmacology, Medical School, University of Athens, Athens, Greece. saranteas@ath.forthnet.gr
Mourouzis
Constantinos
C
Anagnostopoulou
Sophia
S
Danis
Kostas
K
Tachmintzis
Annete
A
Rallis
George
G
D000779:Anesthetics, Local / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D008012:Lidocaine / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008334:Mandible / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding; D011897:Random Allocation; D051381:Rats; D018709:Statistics, Nonparametric; D014018:Tissue Distribution
D000779:Anesthetics, Local; D002250:Carbon Radioisotopes; D008012:Lidocaine; D002251:Carbon Tetrachloride