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Lidocaine and Monoethylglycinexylidide Serum Determinations to Analyze Liver Function of Cirrhotic Patients After Oral Administration

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Abstract

Our aim was to compare standard liver functiontests (serum bilirubin, serum albumin and prothrombinconcentration), with lidocaine andmonoethylglycinexylidide pharmacokinetic parameters,after oral lidocaine administration, to assess hepatic function ofcirrhotic individuals. Twenty-one consecutive cirrhoticpatients, nine consecutive acute hepatitis patients, andnine healthy individuals received oral lidocaine. Lidocaine and monoethylglycinexylidide serumconcentrations were determined by the TDx system.Cirrhotic patients had higher lidocaine and lowermonoethylglycinexylidide serum concentrations anddifferences in its pharmacokinetic variables, compared tocontrol and hepatitis groups (P < 0.05). Sensitivityof lidocaine serum determinations (100%) was greaterthan sensitivity of serum bilirubin (57%), serum albumin (62%), and prothrombin concentrations(43%) and monoethylglycinexylidide serum concentrations(57%) in differentiating cirrhotic individuals fromcontrols. In conclusion, after oral administration, lidocaine and monoethylglycinexylididepharmacokinetic parameters are significantly altered incirrhotic patients compared to normal and acutehepatitis subjects. Lidocaine pharmacokinetic parameterswould be better than those ofmonoethylglycinexylidide and standard liver functiontests in the evaluation of liver function of cirrhoticpatients.

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REFERENCES

  1. Bircher J: Quantitative assessment of deranged hepatic function: A missed opportunity? Semin Liver Dis 3:275-284, 1983

    Google Scholar 

  2. McIntyre N: The limitations of conventional liver function tests. Semin Liver Dis 3:265-270, 1983

    Google Scholar 

  3. Tygstrup N: Assessment of liver function: Principles and practice. J Gastroenterol Hepatol 5:468-482, 1990

    Google Scholar 

  4. Barstow L, Small R: Liver function assessment by drug metabolism. Pharmacotherapy 10:280-288, 1990

    Google Scholar 

  5. Oellerich M, Raude E, Burdelski M, Schulz M, Schmidt F, Ringe B, Lamesh P, Pichlmayr R, Raith H, Scheruhn M, Wrenger M, Wittekind C: Monoethylglycinexylidide formation kinetics: A novel approach to assessment of liver function. J Clin Chem Clin Biochem 25:845-853, 1987

    Google Scholar 

  6. Bargetzi M, Aoyama T, Gonzalez F, Meyer U: Lidocaine metabolism in human live microsomes by cytochrome P450IIIA4. Clin Pharmacol Ther 46:521-527, 1989

    Google Scholar 

  7. Boyes RN, Scott DB, Jebson PJ, Godman MJ, Julian DG: Pharmacokinetics of lidocaine in man. Clin Pharmacol Ther 12:105-116, 1971

    Google Scholar 

  8. Oellerich M, Burdelski M, Lautz HU, Schulz M, Schmidt F W, Herrmann H: Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis. Ther Drug Monit 12:219-226, 1990

    Google Scholar 

  9. Oellerich M, Burdelski M, Lautz HU, Binder L, Pichlmayr R: Predictors of one-year pre transplant survival in patients with cirrhosis. Hepatology 14:1029-1034, 1991

    Google Scholar 

  10. Burdelski M, Oellerich M, Lamesch P, Raude E, Ringe P, Neuhaus S, Bortfeld S, Kammerling C, Raith H, Scheruhn M, Westphal C, Worm M, Pichlmayr R: Evaluation of quantitative liver function tests in liver donors. Transplant Proc 19:3838-3839, 1987

    Google Scholar 

  11. Burdelski M, Oellerich M, Raude E, Lamesch P, Ringe B, Raith B, Scheruhn M, Westphal M, Worm M, Bortfeld M, Schulz M, Wittekind C, Hoyer P, Pichlmayr R: A novel approach to assessment of liver function in donors. Transplant Proc 20:591-593, 1988

    Google Scholar 

  12. Schroeder TJ, Gremse DA, Mansour ME, Theuerling AW, Brunson ME, Ryckman FC, Suchy FJ, Penn I, Alexander JW, Pesce AJ, First MR, Balistreri WF: Lidocaine metabolism as an index of liver function in hepatic transplant donors and recipients. Transplant Proc 21:2299-2301, 1989

    Google Scholar 

  13. Oellerich M, Burdelski M, Ringe B, Lamesch P, Gubernatis G, Bunzendahl H, Pichlmayr R, Herrmann H: Lignocaine metabolite formation as a measure of pre-transplant liver function. Lancet 1:640-642, 1989

    Google Scholar 

  14. Gremse D, A-Kader HH, Schroeder TJ, Balistreri WF: Assessment of lidocaine metabolite formation as a quantitative liver function test in children. Hepatology 12:565-569, 1990

    Google Scholar 

  15. Meyer-Wyss B, Renner E, Luo H, Scholer A: Assessment of lidocaine metabolite formation in comparation with other quantitative liver function tests. J Hepatol 19:133-139, 1993

    Google Scholar 

  16. Huang YS, Lee SD, Deng JF, Wu JC, Lu RH, Lin YF, Wang YJ, Lo KJ: Measuring lidocaine metabolite monoethylglycinexylidide as a quantitative index of hepatic function in adults with chronic hepatitis and cirrhosis. J Hepatol 19:140-147, 1993

    Google Scholar 

  17. Arrigoni A, Gindro T, Aimo G, Capello N, Meloni A, Benedetti P, Molino GP, Verme G, Rizzetto M: Monoe thylglicinexylidide test: A prognostic indicator of survival in cirrhosis. Hepatology 20:383-387, 1994

    Google Scholar 

  18. Shiffman M, Luketic VA, Sanyal AJ, Duckworth PF, Purdum PP, Contos MJ, Mills AS, Edinboro LE, Poklis A: Hepatic lidocaine metabolism and liver histology in patients with chronic hepatitis and cirrhosis. Hepatology 19:933-940, 1994

    Google Scholar 

  19. Eisinger AJ, Hellier MD: Oral lignocaine. Lancet 2:1303, 1969

    Google Scholar 

  20. Parkinson PI, Margolin L: Oral lignocaine: Its absorption and effectiveness in ventricular arrhythmia control. Br Med J 2:29-30, 1970

    Google Scholar 

  21. Rowland M, Thomson PD, Guichard A, Melmon KL: Disposition kinetics of lidocaine in normal subjects. Ann NY Acad Sci 179:383-397, 1971

    Google Scholar 

  22. Huet PM, LeLorier J, Pomier G, Marleau D: Bioavailability of lidocaine in normal volunteers and cirrhotic patients. Gastroenterology 75:969, 1978

    Google Scholar 

  23. Boyes R, Adams H, Duce B: Oral absorption kinetics of lidocaine hydrochloride in dogs. J Pharmacol Exp Ther 174:1-8, 1970

    Google Scholar 

  24. Keenaghan J, Boyes R: The tissue distribution, metabolism and excretion of lidocaine in rats, guinea pigs, dogs and man. J Pharmacol Exp Ther 180:454-463, 1972

    Google Scholar 

  25. Watkins P: Role of cytochromes P450 in drug metabolism and hepatotoxicity. Semin Liver Dis 10:235-250, 1990

    Google Scholar 

  26. Colli A, Buccino G, Cocciolo M, Parravicini R, Scaltrini G: Disposition of a flow-limited drug (lidocaine) and a metabolic capacity-limited drug (theophylline) in liver cirrhosis. Clin Pharmacol Ther 44:642-649, 1988

    Google Scholar 

  27. Ritchie J, Greene N: Anestésicos locales. In Las bases famacológicas de la terapéutica. A Goodman Gilman, T Rall, A Nies, P Taylor (eds). Buenos Aires, Editorial Panamericana, 1991, pp 313-331

    Google Scholar 

  28. Zoppi L, Fumagalli C: Improved measurement of MEGX in serum with the Abbott TDx. Clin Chem 38:441-442, 1992

    Google Scholar 

  29. Shumaker R: PKCALC: A basic interactive computer program for statistical and pharmacokine tic analysis of data. Drug Metab Rev 17:331-348, 1986

    Google Scholar 

  30. BMDP Statistical Software, Inc. Berkeley, University of California, 1992

  31. Fenyves D, Gariepy L, Villeneuve J-P: Clearance by the liver in cirrhosis. I. Relationship between propranolol metabolism in vitro and its extraction by the perfused liver in the rat. Hepatology 17:301-306, 1993

    Google Scholar 

  32. Gariepy L, Fenyves D, Kassissia I, Villeneuve J-P: Clearance by the liver in cirrhosis. II. Characterization of propranolol uptake with the multiple-indicator dilution technique. Hepatology 18:823-831, 1993

    Google Scholar 

  33. Branch RA, Shand DG: Propranolol disposition in chronic liver disease: A physiologic approach. Clin Pharmacokinet 1:264-279, 1976

    Google Scholar 

  34. Huet PM, Villeneuve JP: Determinations of drug disposition in patients with cirrhosis. Hepatology 3:913-918, 1983

    Google Scholar 

  35. Watkins PB, Murray SA, Winkelman LG, Heuman DM, Wrighton SA, Guzelian PS: Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. J Clin Invest 83:688-697, 1989

    Google Scholar 

  36. Meyer B, Luo H, Bargetzi M, Renner EL, Stalder GA. Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: Support for the intact-hepatocyte theory. Hepatology 13:475-481, 1991

    Google Scholar 

  37. Lown K, Kolars J, Turgeon K, Merion R, Wrighton S, Watkins PB: The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease. Clin Pharmacol Ther 51:229-238, 1992

    Google Scholar 

  38. Sawchenko P, Friedman M: Sensory functions of the liver―a review. Am J Physiol 236:R5-R20, 1992

    Google Scholar 

  39. Gumucio J, Chianale J: Liver cell heterogeneity and liver function. In The Liver: Biology and Pathobiology. I Arias, W Jakoby, H Popper, D Schachter, D Shafritz (eds). New York, Raven Press, 1988, pp 931-947

    Google Scholar 

  40. Schaffner F, Popper H: Capillarization of hepatic sinusoids in man. Gastroenterology 44:239-242, 1963

    Google Scholar 

  41. Orrego H, Medline A, Blendis L, Rankin J, Kreaden DA: Collagenisation of the Dissespace in alcoholic liver disease. Gut 20:673-679, 1979

    Google Scholar 

  42. Martinez-Hernandez A, Martinez J: The role of capillarization in hepatic failure: Studies in carbon tetrachloride-induced cirrhosis. Hepatology 14:864-874, 1992

    Google Scholar 

  43. Huet P-M, Pomier-Layrargues G, Villeneuve JP, Varin F, Viallet A: Intrahepatic circulation in liver disease. Semin Liver Dis 6:277-286, 1986

    Google Scholar 

  44. Varin F, Huet P-Michel: Hepatic microcirculation in the perfused cirrhotic rat liver. J Clin Invest 76:1904-1912, 1985

    Google Scholar 

  45. Villeneuve JP, Dagenais M, Huet P-Michel, Roy A, Lapointe R, Marleau D: The hepatic microcirculation in the isolated perfused human liver. Hepatology 23:24-31, 1996

    Google Scholar 

  46. Pessayre D, Lebrec D, Descatoire V, Peignoux M, Benhamou JP: Mechanism for reduced drug clearance in patients with cirrhosis. Gastroenterology 74:566-571, 1978

    Google Scholar 

  47. Huet P-M, Pomier G, Clement L, LeLorier J: Uptake of labeled lidocaine by the intact liver. Clin Res 26:835A, 1978

    Google Scholar 

  48. Huet P-M, Leclair B: Hepatic handling of lidocaine during a single passage through the liver in dogs. Clin Invest Med 4:7B, 1981

    Google Scholar 

  49. Bennett P, Aarons L, Bending M, Steiner J, Rowland M: Pharmacokine tics of lidocaine and its dee thylated metabolite: dose and time dependency studies in man. J Pharmacokinet Biopharmacol 10:265-281, 1982

    Google Scholar 

  50. Chapman R, Angus P: Effect of liver disease on the gastrointestinal tract. In Oxford Textbook of Clinical Hepatology. N McIntyre, J Benhamou, J Bircher, M Rizzetto, J Rodes (eds). Oxford, Oxford University Press, 1991, pp 1240-1245

    Google Scholar 

  51. Kolars JC, Schmiedlin-Ren P, Shuetz JD, Fang C, Watkins PB: Identification of rifampicin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 90:1871-1878, 1992

    Google Scholar 

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Authors
  1. Alberto E. Munoz
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  2. Carlos Miguez
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  3. Modesto Rubio
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  4. Maria Bartellini
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  5. Diana Levi
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  6. Ana Podesta
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  7. Viviana Niselman
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  8. Ruben Terg
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Munoz, A.E., Miguez, C., Rubio, M. et al. Lidocaine and Monoethylglycinexylidide Serum Determinations to Analyze Liver Function of Cirrhotic Patients After Oral Administration. Dig Dis Sci 44, 789–795 (1999). https://doi.org/10.1023/A:1026630313038

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