PURPOSE: This study was designed to investigate the disposition of (14)C-lidocaine in serum and tissues in rats with liver dysfunction. MATERIALS AND 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. CONCLUSION: 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.
PURPOSE: This study was designed to investigate the disposition of (14)C-lidocaine in serum and tissues in rats with liver dysfunction. MATERIALS AND 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. CONCLUSION: 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.
Authors: A Kotsiou; M Tsamouri; S Anagnostopoulou; M Tzivras; E Vairactaris; C Tesseromatis Journal: Eur J Drug Metab Pharmacokinet Date: 2006 Apr-Jun Impact factor: 2.441