Summary
This study was designed to investigate the binding of clonidine to liver protein as well as the possible interactions with non-steroid anti-inflammatory drugs (NSAIDs) during the binding process in the rabbit.
The binding of clonidine to slices (S) and homogenized slices (H) was estimated by a radioisotopic method following incubation with a mixture of cold and3H-labelled clonidine in Ringer solution at 37°C for 360 min.
The binding of clonidine was assessed in the absence and presence of the following NSAIDs: flurbiprofen, ketoprofen, ibuprofen and acetylsalicylic acid.
The results showed that the percentage of clonidine binding did not differ between intact and homogenized slices. The addition of all NSAIDs but ibuprofen, significantly decreased the protein binding of clonidine both in intact and homogenized liver slices.
This finding could be attributed to the different affinity of ibuprofen for liver protein compared to the remaining NSAID’s which may arise from a number of chemical properties including its dual Pka values.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Evers A., Crowder M. (2001): General Anesthetics. In Hardman G, Limbird L, eds. Goodman and Gilman’s, the pharmacological basis of therapeutics. New York: McGraw-Hill, 358.
Ubeaud G., Schiller CD., Hurbin F., Jaeck D., Coassolo P. (2001): Comparison of the stability of some major cytochrome P-450 and cojugation reaction in rat, dog and human hepatocyte monolayers. Eur. J. Drug. Metab. Pharmacokin., 26, 37–45.
Andrade SE., Martinez C., Walker AM. (1998): Comparative safety evaluation of non-narcotic analgesics. J. Clin. Epidemiol., 51, 1357–1365.
Kurz H., Trunk H., Weitz B. (1977): Evaluation of methods to determine protein. Protein binding of drugs. Arzneim. Forsch., 27, 1373–1380.
Stoelting KR. (1999): Antihypertensive drugs. In Stoelting KR eds. Pharmacology and physiology in anesthetic practice. Philadelphia: Lipincott-Williams & Wilkins, 304–307.
Kurz H. (1966): Die Permeation von Giften in die Leber. Eingeschhaften der Zellmembran. Arch. Pharmac (Naunym-Schmied), 254, 33–44.
Bickel M.H., Steele J.W. (1974): Binding of basic and acidic drugs to the rat subcellural fractions. Chem. Biol. Interactions, 8, 151–162.
Filous N., Fichtl B., Kurz H. (1976): Binding of drugs to muscle tissue. Arch. Pharmacol., 290 R 46.
Fichtl B., Kurz H. (1980): Does determination of drug binding in homogenized tissue reflect binding in the intact organ. Arch. Pharmacol (Naunym-Schimied), 311 R3.
Tesseromatis C., Fichtl B., Kurz H. (1987): Binding of non-steroid antiflammatory drugs and warfarin to liver tissue of rabbits in vitro. Eur. J. Drug. Metab. Pharmacokin, 12, 161–167.
Bickel MH., Steele JW. (1974): Binding of basic and acidic drugs to the rat tissue subcellular fraction. Chem Biol Interact., 8, 151–62.
Kurz H., Fichtl B. (1983): Binding of drugs to tissues. Drug Metab. Rev., 14(3), 467–510.
Nishika K., Mikawa K., Shiga M., Takao V., Mackawa N., Obara H. (2000): Diclofenac and fluriprofen with or without clonidine for postoperative analgesic in children undergoing elective ophtallmological surgery. Paediatr Anaesth., 10(6), 45–51.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tesserommatis, C., Saranteas, T., Chatzijanni, E. et al. Modifications of clonidine binding to rabbit liver protein under the influence of non-steroid-anti-inflammatory drugsin vitro . Eur. J. Drug Metab. Pharmacokinet. 28, 245–247 (2003). https://doi.org/10.1007/BF03190492
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03190492