14C-Lidocaine Disposition in Serum and Tissues of Normal and Liver Diseased Rats

PurposeThis study was designed to investigate the disposition of 14C-lidocaine in serum and tissues in rats with liver dysfunction.Materials and MethodsEighteen male rats were randomly divided into 2 groups. Group A was considered as control while group B underwent liver damage by administrating CCl4 0.4 mg/kg twice a week for 6 weeks. Both groups received 5 doses of 2.5 mg/kg lidocaine mixture (labeled 14C-lidocaine and nonlabeled). The rats were killed 2 hours after the last dose. Total lidocaine levels (14C-lidocaine and 14C-lidocaine metabolite concentrations) as well as the percent of total lidocaine-bound fractions in tissues were measured.Results14C-lidocaine concentrations were significantly increased in the serum (9.4 ± 0.4 μg/mL), heart (7.8 ± 2 μg/gL), and mandible (0.97 ± 0.01μg/g) in diseased rats as compared with normal rats (serum, 5.3 ± 1.7 μg/mL; heart, 4.2 ± 0.9 μg/g; mandible, 0.68 ± 0.02 μg/g, respectively). 14C-lidocaine bound fractions in the mandible and heart did not show any significant differences between the 2 groups. Instead, 14C-lidocaine bound fractions in serum were significantly reduced in diseased animals as opposed to normal ones.ConclusionWe concluded that liver dysfunction can modify 14C-lidocaine concentrations in the serum and tissues without altering the lidocaine binding properties in the mandible and heart.