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Órgano Oficial de la Asociación Mexicana de Hepatología

2003, Number 4

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Ann Hepatol 2003; 2 (4)

Ketorolac pharmacokinetics in experimental cirrhosis by bile duct ligation in the rat

Rivera-Espinosa L, Muriel P, Ordaz GM, Pérez-Urizar J, Palma-Aguirre A, Castañeda-Hernández G

Language: English
References: 33
Page: 175-181
PDF size: 126.77 Kb.


Text Extraction

The purpose of the present work was to study the pharmacokinetics of ketorolac, a poorly metabolized drug, in experimental cirrhosis. Cirrhosis was induced by bile duct ligation (BDL) for four weeks in male Wistar rats. Ketorolac was given intravenously (1 mg/kg ) or orally (3.2 mg/kg) to control (sham-operated) and BDL-rats. Determination of ketorolac in plasma was carried out by HPLC and estimation of pharmacokinetic parameters was performed by non-compartmental analysis. Indicators of liver damage and liver fibrosis were significantly increased (p ‹ 0.05) in BDL compared to control rats. Experimental cirrhosis did not induce any significant alteration in intravenous ketorolac pharmacokinetics. Volume of distribution, clearance, AUC and t1/2 were similar in BDL and control animals. Notwithstanding, oral ketorolac bioavailability was significantly altered in BDL rats. AUC and Cmax were reduced, while tmax was prolonged, suggesting that both, the extent and the rate of ketorolac absorption were decreased. Results show that liver cirrhosis may result in significant pharmacokinetic alterations, even for poorly bio-transformed drugs, but that alterations may vary with the route of administration. In conclusion, uncritical generalizations on the effect of liver damage on drug kinetics should be avoided and systematic studies for every drug and every route of administration are thus recommended.


REFERENCES

  1. Flores-Murrieta FJ, Granados-Soto V. Pharmacologic properties of ketorolac tromethamine: a potent analgesic drug. Rev 1996; 2: 75-90.

  2. Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 139-188.

  3. Rooks WH, Maloney PJ, Tolomonis AJ, Wallace MB, Schuler ME. The analgesic and anti-inflammatory profile of (+)-5-benzoil-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (RS-37619). Agents and Actions 1982; 12: 684-690.

  4. Domer F. Characterization of the analgesic activity of ketorolac in mice. Eur J Pharmacol 1990; 177: 127-135.

  5. Granados-Soto V, Flores-Murrieta FJ, Castañeda-Hernández G, López-Muñoz FJ. Evidence for the involvement of nitric oxide in the antinociceptive effect of ketorolac. Eur J Pharmacol 1995; 277: 281-284.

  6. Lázaro-Ibañez GG, Torres-López JE, Granados-Soto V. Participation of the nitric oxide-cyclic GMP-ATP-sensitive K+ channel pathway in the antinociceptive action of ketorolac. Eur J Pharmacol 2001; 426: 41-46.

  7. Granados-Soto V, López-Muñoz J, Hong E, Flores-Murrieta. Relationship between pharmacokinetics and the analgesic effect of ketorolac in the rat. J Pharmacol Exp Ther 1995; 272: 352-356.

  8. Mandema JW, Stanski DR. Population pharmacodynamic model for ketorolac analgesia. Clin Pharmacol Ther 1996; 60: 619-635.

  9. Pérez-Urizar J, Granados-Soto V, Castañeda-Hernández G, Hong E, González C, Martínez JL, Flores-Murrieta FJ. Analgesic efficacy and bioavailability of ketorolac in postoperative pain: a probability analysis. Arch Med Res 2000; 31: 191-196.

  10. Estes LL, Fuhs DW, Heaton AH, Butwinick CS. Gastric ulcer perforation associated with the use of injectable ketorolac. Ann Pharmacother 1993; 27: 42-43.

  11. Kenny GNC. (1992) Potential renal, haematological and allergic adverse effects associated with nonsteroidal anti-inflammatory drugs. Drugs 1992; 44: 5: 31-37.

  12. Boras-Uber LA, Brackett NC. (1992) Ketorolac-induced acute renal failure. Am J Med 1992; 450-452.

  13. Quan DJ, Kayser SR. Ketorolac induced acute renal failure following a single dose. Clin Toxicol 1994; 32: 305-309.

  14. Rowland M, Tozer TN. (1995) Clinical Pharmacokinetics: Concepts and applications, 3rd ed., Williams & Wilkins, Media, PA. 1995; 248-266.

  15. Pages LJ, Martínez JJ, Garg DC, Yee JP, Mroszczac ES, Renneke GA, Weidler DJ. Pharmacokinetics of ketorolac tromethamine in hepatically impaired versus young healthy subjects. J Clin Pharmacol 1987; 27: 724.

  16. Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet 1992; 23: 415-27.

  17. Favari L, Castañeda-Hernández G, Hoyo-Vadillo C. Naproxen pharmacokinetics and pharmacodynamics in acute experimental hepatitis. Arzneim Forsch 1993; 43: 675-679.

  18. Groszmann RJ, Loureiro-Silva MR, Tsai MH. The biology of portal hypertension. In The liver biology and pathobiology. Edited by I.M. Arias JL, Boyer FV, Chisari N, Fausto D, Schachter DA. Shafritz. Lippincott Williams & Wilkins Publishers, Philadelphia, P.A. 2001; 679-719.

  19. Shibayama Y, Nakata K. Haemodynamic alterations and their morphological basis in biliary obstruction. Liver 1992; 12: 175-178.

  20. Van de Casteele M, Sagesser H, Zimmermann H, Reichen J. Characterization of portal hypertension models by microspheres in anesthetized rats: a comparison of liver flow. Pharmacol Ther 2001; 90: 35-43.

  21. Castañeda-Hernández G, Favari L, Hoyo-Vadillo C. Relationship between naproxen plasma concentration and its antiinflammatory effect in experimental hepatitis. Arzneim Forsch 1995; 45: 585-589.

  22. Norma Oficial Mexicana NOM-062-ZOO-1999.

  23. Canadian Council on Animal Care. Guide to the care and use of experimental animals. Canadian Council of animal Care. Ottawa, Ont. 1993. http://www.ccac.ca/english/gui_pol/guides/english/toc_v1.htm

  24. Fernández-Martínez E, Morales-Ríos MS, Pérez-Álvarez V, Muriel P. Effects of thalidomide and 3-phtalimido-3-(3,4-dimethoxyphenyl)-propanamide on bile duct obstruction-induced cirrhosis in the rat. Drug Dev Res 2001; 54: 209-218.

  25. Kountaras J, Biling BH, Scheuer PJ. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol 1984; 65: 305-308.

  26. Glossman M, Neville DM. Gamma-glutamyl transferase in kidney brush border membranes. Febs Lett 1972; 19: 340-344.

  27. Reitman S, Frankel SA. A colorimetric method for the determination of rum glutamic oxaloacetic pyruvic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28: 56-63.

  28. Muriel P. Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride. Biochem Pharmacol 1998; 56: 773-779.

  29. Flores-Murrieta FJ, Granados-Soto V, Hong E. Determination of ketorolac in blood and plasma samples by high-performance liquid chromatography. Boll Chim Farm 1994; 133: 588-591.

  30. Rosen HR, Keeffe EB. Evaluation of abnormal liver enzymes, use of liver test, and the serology of viral hepatitis. In: Liver disease Diagnosis and management. Edited by B. Di Bisceglie. Churchill Livingstone, New York, NY. 2000; 24-35.

  31. Granados-Soto V, Flores-Murrieta FJ. Pharmacokinetics of oral ketorolac in the rat. Methods Find Exp Clin Pharmacol 1995; 17: 535-538.

  32. Mroszczac EJ, Jung D, Yee J, Bynum L, Sevelius H, Massey I. Ketorolac tromethamine pharmacokinetics and metabolism after intravenous, intramuscular and oral administration in humans and animals. Pharmacotherapy 1990; 10: 33S-39S.

  33. Avdeef A. Physicochemical profiling (solubility, permeability and charge state). Curr Top Med Chem 2001; 1: 277-351.




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