Klinische Wochenschrift

, Volume 67, Issue 1, pp 6–15 | Cite as

Correlation of caffeine elimination and child's classification in liver cirrhosis

  • A. Holstege
  • M. Staiger
  • K. Haag
  • W. Gerok
Originalien
Received:
Revised:
Accepted:

Summary

Apparent pharmacokinetic parameters of caffeine elimination from the circulation were determined in 27 patients with histologically confirmed liver cirrhosis, 8 patients with miscellaneous liver disease, and 8 patients with other than liver disease. The usefullness of this quantitative test to assess the severity of liver cirrhosis was compared to the Child-Turcotte or Child-Pugh classification score as well as to the galactose elimination capacity of these patients. Using reversed-phase high pressure liquid chromatography caffeine, paraxanthine, theophylline, and theobromine were analysed in blood plasma collected before and after an oral dose of caffeine. Compared to apparent caffeine pharmacokinetics in patients with normal livers or miscellaneous liver disease, cirrhosis was characterized by a statistically significant reduction in apparent caffeine clearance and prolongation in half-life. The reduced apparent plasma disappearance rate of caffeine in cirrhotics was related to the retarded formation of paraxanthine which was the main metabolite of caffeine in blood plasma both in the absence or presence of liver disease. The apparent caffeine clearance in cirrhosis decreased with increasing Child-Turcotte classification score: Child's class A patients differed significantly from Child's class B or Child's class C patients, whereas the difference between Child's class B and C patients did not reach statistical significance (Wilcoxon's rank test). In addition there was a strong correlation between the Child-Pugh classification score and apparent caffeine clearance (P<0.001). However, no correlation existed between Child's classification and galactose elimination capacity. Our data emphasize the value of the Child-Turcotte or Child-Pugh classification in assessing the severity of liver cirrhosis in a simpler and less time-consuming way than using quantitative liver function tests.

Key words

Child's classification Caffeine elimination Liver disease 

Abbreviations

AUC

Area under curve

Cl

apparent caffeine clearance

GEC

galactose elimination capacity

V0

distribution volume

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References

  1. 1.
    Abbott PJ (1986) Caffeine: a toxicological overview. Med J Aust 145:518–521Google Scholar
  2. 2.
    Barbare JC, Poupon RE, Jaillon P, Prod'homme S, Darnis F, Poupon RY (1985) Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis. J Hepatol 1:253–259Google Scholar
  3. 3.
    Bircher J (1986) Assessment of prognosis in advanced liver disease: to score or to measure, that's the question. Hepatology 6:1036–1037Google Scholar
  4. 4.
    Bircher J, Blankart R, Halpern A, Häcki W, Laissue J, Preisig R (1973) Criteria for assessment of functional impairment in patients with cirrhosis of the liver. Eur J Clin Invest 3:72–85Google Scholar
  5. 5.
    Blanchard J, Sawers SJA (1983) The absolute bioavailability of caffeine in man. Eur J Clin Pharmacol 24:93–98Google Scholar
  6. 6.
    Bonati M, Latini R, Galletti F, Young JF, Tognoni G, Garattini S (1982) Caffeine disposition after oral doses. Clin Pharmacol Ther 32:98–106Google Scholar
  7. 7.
    Broughton LJ, Rogers HJ (1981) Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmac 12:155–159Google Scholar
  8. 8.
    Caesar U (1983) Koffein bei Lebererkrankungen. Thesis, WürzburgGoogle Scholar
  9. 9.
    Child CG, Turcotte JG (1964) Surgery and portal hypertension. In: Child CG (ed) The liver and portal hypertension. WB Saunders, Philadelphia, pp 50–62Google Scholar
  10. 10.
    Christensen E, Schlichting P, Fauerholdt L, Gluud C, Andersen PK, Juhl E, Poulsen H, Tygstrup N (1984) Prognostic value of Child-Turcotte criteria in medically treated cirrhosis. Hepatology 4:430–435Google Scholar
  11. 11.
    Christensen E, Schlichting P, Kragh Anderson P, Fauerholdt L, Schou G, Vestergaard Pedersen B, Juhl E, Poulsen H, Tygstrup N, The Copenhagen Study Group for Liver Diseases (1986) Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables. Scand J Gastroenterol 21:163–174Google Scholar
  12. 12.
    Conn HO (1981) A peek at the Child-Turcotte classification. Hepatology 1:673–676Google Scholar
  13. 13.
    Desmond PV, Patwardhan RV, Johnson RF, Schenker S (1980) Impaired elimination of caffeine in cirrhosis. Dig Dis Sci 25:193–197Google Scholar
  14. 14.
    Infante-Rivard C, Esnaola S, Villeneuve J-P (1987) Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics. Hepatology 7:660–664Google Scholar
  15. 15.
    Jenne JW, Chick TW, Miller BA, Dee Strickland R (1974) Effect of congestive heart failure on the elimination of theophylline (Abstract). J Allergy Clin Immunol 53:80Google Scholar
  16. 16.
    Jost G, Wahlländer A, Von Mandach U, Preisig R (1987) Overnight salivary caffeine clearance: a liver function test suitable for routine use. Hepatology 7:338–344Google Scholar
  17. 17.
    Kalow W (1985) Variability of caffeine metabolism in humans. Drug Res 35:319–324Google Scholar
  18. 18.
    Kamimori GH, Somani SM, Knowlton RG, Perkins RM (1987) The effects of obesity and exercise on the pharmacokinetics of caffeine in lean and obese volunteers. Eur J Clin Pharmacol 31:595–600Google Scholar
  19. 19.
    Kotake AN, Schoeller DA, Lambert GH, Baker AL, Schaffer DD, Josephs H (1982) The caffeine CO2 breath test: dose response and route ofN-demethylation in smokers and nonsmokers. Clin Pharmacol Ther 32:261–269Google Scholar
  20. 20.
    Lambert GH, Schoeller DA, Kotake AN, Flores C, Hay D (1986) The effect of age, gender, and sexual maturation on the caffeine breath test. Dev Pharmacol Ther 9:375–388Google Scholar
  21. 21.
    Lelo A, Miners JO, Robson R, Birkett DJ (1986) Assessment of caffeine exposure: caffeine content of beverages, caffeine intake, and plasma concentrations of methylxanthines. Clin Pharmacol Ther 39:54–59Google Scholar
  22. 22.
    Lelo A, Birkett DJ, Robson RA, Miners JO (1986) Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. Br J Clin Pharmacol 22:177–182Google Scholar
  23. 23.
    Lelo A, Miners JO, Robson RA, Birkett DJ (1986) Quantitative assessment of caffeine partial clearances in man. Br J Clin Pharmacol 22:183–186Google Scholar
  24. 24.
    Mangione A, Imhoff TE, Lee RV, Shum LY, Jusko WJ (1978) Pharmacokinetics of theophylline in hepatic disease. Chest 73:616–622Google Scholar
  25. 25.
    McLean AEM (1975) The measurement of liver injury and protection, with special reference to paracetamol, dimethylnitrosamine and carbon tetrachloride. In: Keppler D (ed) Pathogenesis and mechanisms of liver cell necrosis. MTP Press, Lancaster, pp 119–127Google Scholar
  26. 26.
    Onrot J, Shaheen O, Biaggioni I, Goldberg MR, Feely J, Milkinson GR, Hollister AS, Robertson D (1986) Reduction of liver plasma flow by caffeine and theophylline. Clin Pharmacol Ther 40:506–510Google Scholar
  27. 27.
    Orrego H, Israel Y, Blake JE, Medline A (1983) Assessment of prognostic factors in alcoholic liver disease: toward a global quantitative expression of severity. Hepatology 3:896–905Google Scholar
  28. 28.
    Parsons WD, Neims AH (1978) Effect of smoking on caffeine clearance. Clin Pharmacol Ther 24:40–45Google Scholar
  29. 29.
    Pathwardhan RV, Desmond PV, Johnson RF, Schenker S (1980) Impaired elimination of caffeine by oral contraceptive steroids. J Lab Clin Med 95:603–608Google Scholar
  30. 30.
    Piafsky KM, Sitar SD, Rangno RE, Ogilvie RJ (1977) Theophylline kinetics in acute pulmonary edema. Clin Pharmacol Ther 21:310–316Google Scholar
  31. 31.
    Preisig R (1985) Fremdsubstanzen als Indikatoren der Leberfunktion. Schweiz Med Wochenschr [Suppl 19] 115:36–42Google Scholar
  32. 32.
    Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649Google Scholar
  33. 33.
    Reichen J, Le M (1986) Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver. J Clin Invest 78:448–455Google Scholar
  34. 34.
    Renner E, Wahlländer A, Huguenin P, Wietholz H, Preisig R (1983) Coffein — ein ubiquitärer Indikator der Leberfunktion. Schweiz Med Wochenschr 113:1074–1081Google Scholar
  35. 35.
    Renner E, Wietholz H, Huguenin P, Arnaud MJ, Preisig R (1984) Caffeine: a model compound for measuring liver function. Hepatology 4:38–46Google Scholar
  36. 36.
    Ritschel WA, Hussain AS, Wetzelsberger N, Lücker PW (1985) Theophylline-ranitidine drug interaction in the beagle dog. Methods Find Exp Clin Pharmacol 7:631–636Google Scholar
  37. 37.
    Statland BE, Demas TJ (1980) Serum caffeine half-lives. Healthy subjects vs patients having alcoholic hepatic disease. Am J Clin Pathol 73:390–393Google Scholar
  38. 38.
    Stavric B, Klassen R (1984) Automated high-performance liquid chromatographic assay for monitoring caffeine and its meabolites in biological fluids of monkeys consuming caffeine. J Chromatogr 310:107–118Google Scholar
  39. 39.
    Tang-Liu DD, Williams RL, Riegelman S (1983) Disposition of caffeine and its metabolites in man. J Pharm Exp Ther 224:180–185Google Scholar
  40. 40.
    Tygstrup N (1966) Determination of hepatic elimination of galactose by single injection. Scand J Clin Lab Invest [Suppl 92] 18:118–125Google Scholar
  41. 41.
    Villeneuve J-P, Infante-Rivard C, Ampelas M, Pomier-Layrargues G, Muet P-M, Marleau DT (1986) Prognostic value of the aminopyrine breath test in cirrhotic patients. Hepatology 6:928–931Google Scholar
  42. 42.
    Wahlländer A, Renner E, Preisig R (1985) Fasting plasma caffeine concentration. A guide to the severity of chronic liver disease. Scand J Gastroenterol 20:1133–1141Google Scholar
  43. 43.
    Wang T, Kleber G, Stellaard F, Paumgartner G (1985) Caffeine elimination: a test of liver function. Klin Wochenschr 63:1124–1128Google Scholar
  44. 44.
    Wietholz H, Voegelin M, Arnaud MJ, Bircher J, Preisig R (1981) Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. Eur J Clin Pharmacol 21:53–59Google Scholar
  45. 45.
    Zilly W, Caesar U, Staib AH, Heusler H, Richter E (1982) Die Elimination von Koeffein bei Lebererkrankungen. In: Rietbrock N, Woodcock BG, Staib AH (eds) Theophylline and other methylxanthines. Vieweg, Braunschweig, pp 69–75Google Scholar
  46. 46.
    Zilly W, Ziegler M, Richter E (1986) Interaktion zwischen Coffein and Theophyllin. Med Klin 81:560–562Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • A. Holstege
    • 1
  • M. Staiger
    • 1
  • K. Haag
    • 1
  • W. Gerok
    • 1
  1. 1.Abteilung Innere MedizinAlbert-Ludwigs-UniversitätFreiburg

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