14C-Lidocaine Disposition in Serum and Tissues of Normal and Liver Diseased Rats
Purpose
This study was designed to investigate the disposition of 14C-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 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.
Results
14C-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.
Conclusion
We 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.
⁎Senior Research Fellow, Department of Pharmacology, Medical School, University of Athens, Athens, Greece; and Senior Resident, Department of Anesthesiology, General Hospital of Athens “G. Gennimatas,” Athens, Greece
†Oral and Maxillofacial Surgeon and Senior Research Fellow, Division of Oral Pharmacology and Therapeutics, Department of Pharmacology, Medical School, University of Athens, Athens, Greece
‡Associate Professor, Department of Human Anatomy, Medical School, University of Athens, Athens, Greece
§Regional Epidemiologist, Department of Epidemiology, Health Protection Agency East Midlands, Nottingham City Hospital, Nottingham, UK
∥Consultant, Department of Anesthesiology, General Hospital of Athens “G. Gennimatas,” Athens, Greece
¶Senior Hospital Specialist of the Department of Oral & Maxillofacial Surgery, General Hospital of Attica “KAT,” Athens, Greece
Address correspondence and reprint requests to Dr Saranteas: 19 Karatza str and Klemanso 18534 Piraeus, Athens, Greece
ABSTRACT