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Effect of hepatic insufficiency on pharmacokinetics and drug dosing

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Abstract

The liver plays a central role in the pharmacokinetics of many drugs. Liver dysfunction may not only reduce the plasma clearance of a number of drugs eliminated by biotransformation and/or biliary excretion, but it can also affect plasma protein binding which in turn could influence the processes of distribution and elimination. In addition, reduced liver blood flow in patients with chronic liver disease will decrease the systemic clearance of flow limited (high extraction) drugs and portal‐systemic shunting may substantially reduce their presystemic elimination (first‐pass effect) following oral administration. When selecting a drug and its dosage regimen for a patient with liver disease additional considerations such as altered pharmacodynamics and impaired renal excretion (hepatorenal syndrome) of drugs and metabolites should also be taken into account. Consequently, dosage reduction is necessary for many drugs administered to patients with chronic liver disease such as liver cirrhosis.

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References

  1. Howden CW, Birnie GG, Brodie MJ. Drug metabolism in liver disease. Pharmac Ther 1989;40:439–74.

    Google Scholar 

  2. Brouwer KLR, Dukes GE, Powell JR. Influence of liver function on drug disposition. In Evans WE, Schentag JJ and Jusko WJ, eds. Applied pharmacokinetics. Principles of therapeutic drug monitoring (Third edition). Vancouver WA: Applied Therapeutics Inc., 1992;6:1–59.

    Google Scholar 

  3. McLean AJ, Morgan DJ. Clinical pharmacokinetics in patients with liver disease. Clin Pharmacokinet1991;21:42–69

    Google Scholar 

  4. Morgan DJ, McLean AJ. Clinical pharmacokinetic and pharmacodynamic considerations in patients with liver disease. Clin Pharmacokinet 1995;29:370–91.

    Google Scholar 

  5. Rowland M, Tozer TN. Clinical pharmacokinetics. Concepts and applications. Philadelphia: Lea and Febiger, 1989:189–90.

    Google Scholar 

  6. Wilkinson GR. Clearanceapproaches in pharmacology. Pharmacol Rev 1987;39:1–47.

    Google Scholar 

  7. Pond SM, Tozer TN. First-pass elimination: basic concepts and clinical consequences. Clin Pharmacokinet 1984;9:1–25.

    Google Scholar 

  8. Tam YK. Individual variation in first-pass metabolism. Clin Pharmacokinet 1993;25:300–28.

    Google Scholar 

  9. Wilkinson GR. Influence of liver disease on pharmacokinetics. In Evans WE, Schentag JJ and Jusko WJ, eds. Applied pharmacokinetics. Principles of therapeutic drug monitoring.San Francisco, Applied Therapeutics Inc., 1980;19–41.

    Google Scholar 

  10. Neal EA, Meffin PJ, Gregory PB, Blaschke TF. Enhanced bio-availability and decreased clearance of analgesics in patients with cirrhosis. Gastroenterology 1979;77:96–102.

    Google Scholar 

  11. Blaschke TF, Rubin PC. Hepatic first-pass metabolism in liver disease. Clin Pharmacokinet 1979;4:423–32.

    Google Scholar 

  12. Pentikäinen PJ, Neuvonen PJ, Jotell KG. Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver. Eur J Clin Pharmacol 1980;17:275–84.

    Google Scholar 

  13. Bergstrand RH, Wang T, Roden DM, Avant GR, Sutton WW, Siddoway LA, Wolfenden H, Woosley RL, Wilkinson GR, Wood AJJ. Encainide disposition in patients with chronic cirrhosis. Clin Pharmacol Ther 1986;40:148–54.

    Google Scholar 

  14. Janssen U, Walker S, Maier K, von Gaisberg U, Klotz U. Flumazenil disposition and elimination in cirrhosis. Clin Pharmacol Ther 1989;46:317–23.

    Google Scholar 

  15. Homeida M, Jackson L, Roberts CJC. Decreased first-pass metabolism of labetalol in chronic liver disease. Br Med J 1978;2:1048–50.

    Google Scholar 

  16. Pentikäinen PJ, Välisalmi L, Himberg JJ, Crevoisier C. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects.J Clin Pharmacol 1989;29:272–7.

    Google Scholar 

  17. Hasselström J, Eriksson S, Persson A, Rane A, Svensson JO, Säwe J. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol 1990;29:289–97.

    Google Scholar 

  18. Kleinbloesem CH, van Harten J, Wilson JPH, Danhof M, van Brummelen P, Breimer DD. Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration. Clin Pharmacol Ther 1986;40:21–8.

    Google Scholar 

  19. van Harten J, van Brummelen P, Wilson JHP, Lodewijks MTM, Breimer DD. Nisoldipine: kinetics and effects on blood pressure and heart rate in patients with liver cirrhosis after intravenous and oral administration. Eur J Clin Pharmacol 1988;34:387–94.

    Google Scholar 

  20. Branch RA, Kornhauser DM, Shand DG, Wilkinson GR, Wood AJJ. Biological determinants of propranolol disposition in normal subjects and patients with cirrhosis. Br J Clin Pharmacol 1977;4:630P.

    Google Scholar 

  21. Somogyi A, Albrecht M, Kliems G, Schafer K, Eichelbaum M. Pharmacokinetics, bioavailability and ECG response of verapamil in patients with liver cirrhosis. Br J Clin Pharmacol 1981;12:51–60.

    Google Scholar 

  22. Tozer TN. Concepts basic to pharmacokinetics In Rowland M and Tucker G, eds. Pharmacokinetics: theory and methodology. Oxford, Pergamon Press, 1986:29–51.

    Google Scholar 

  23. Tozer TN. Implications of altered plasma protein binding in disease states.In Benet LZ, Massoud N and Gambertoglio JG, eds. Pharmacokinetic basis for drug treatment. New York Raven Press, 1984:173–93.

    Google Scholar 

  24. Blaschke TF. Protein binding and kinetics of drugs in liver disease Clin Pharmacokinet 1977;2:32–44.

    Google Scholar 

  25. Williams RL, Upton RA, Cello JP, Jones RM, Blitstein M, Kelly J, Nierenburg D. Naproxen disposition in patients with alcoholic cirrhosis. Eur J Clin Pharmacol 1984;27:291–6.

    Google Scholar 

  26. Martinez-Hernandez A, Martinez J. The role of capillarization in hepatic failure: studies in carbon tetrachloride-induced cirrhosis. Hepatolog 1991;14:864–74.

    Google Scholar 

  27. Morgan DJ, McLean AJ.Therapeutic implications of impaired hepatic oxygen diffusion in chronic liver disease. Hepatology 1991;14:1280–2.

    Google Scholar 

  28. Howden CW, Birnie GG, Brodie MJ. Drug metabolism in liver disease. Pharmac Ther 1989;40:439–74.

    Google Scholar 

  29. Paintaud G, Bechtel Y, Brientini M-P, Miguet J-P, Bechtel PR. Effects of liver diseases on drug metabolism. Thérapie 1996;51:384–9

    Google Scholar 

  30. Hoyumpa AM, Schenker S. Is glucuronidation truely preserved in patients with liver disease? Hepatology 1991;13:786–95.

    Google Scholar 

  31. Debinski HS, Lee CS, Danks JA, Mackenzie PI, Desmond PV. Localization of 5'-diphosphate-glucuronosyltransferase in human liver injury. Gastroenterology 1995;108:1464–9.

    Google Scholar 

  32. Sonne J, Anderson PB, Loft S, Døssing M, Andreasen F. Glucuronidation of oxazepam is not spared in patients with hepatic encephalopathy. Hepatology 1990;11:951–6.

    Google Scholar 

  33. Macdonald JI, Wallace SM, Mahachai V, Verbeeck RK. Both phenolic and acyl glucuronidation pathways of diflunisal are impaired in liver cirrhosis. Eur J Clin Pharmacol 1992;42: 471–4.

    Google Scholar 

  34. Murray M. P450 enzymes: inhibition mechanisms, genetic regulation and effects of liver disease. Clin Pharmacokinet 1992;23:132–46.

    Google Scholar 

  35. May DG, Arns PA, Richards WO, Porter J, Ryder D, Fleming CM, Wilkinson GR, Branch RA. The disposition of dapsone in cirrhosis. Clin Pharmacol Ther 1992;51:689–700.

    Google Scholar 

  36. Lown K, Kolars J, Turgeon K, Merion R, Wrighton SA, Watkins PB. The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease. Clin Pharmacol Ther 1992;51:229–38.

    Google Scholar 

  37. George J, Murray M, Byth K, Farrell GC. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology 1995;21:120–8.

    Google Scholar 

  38. Krishna DR, Klotz U. Extrahepatic metabolism of drugs in humans. Clin Pharmacokinet 1994;26:144–60.

    Google Scholar 

  39. Kolars JC, Schmiedlin-Ren P, Schuetz JD, Fang C, Watkins PB. Identification of rifampicin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992;90:1871–8.

    Google Scholar 

  40. Kivistö KT, Bookjans G, Fromm MF, Griese EU, Münzel P, Kroemer HK. Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue. Br J Clin Pharmacol 1996;42:387–98.

    Google Scholar 

  41. Mazoit JX, Sandouk P, Scherrmann JM, Roche A. Extrahepatic metabolism of morphine occurs in humans. Clin Pharmacol Ther 1990;48:613–8.

    Google Scholar 

  42. Bodenham A, Quinn K, Park GR. Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth1989;63:380–4.

    Google Scholar 

  43. Lange H, Stephan H, Rieke H, Kellerman M, Sonntag H, Bircher J. Hepatic and extrahepatic disposition of propofol in patients undergoing coronary bypass surgery. Br J Anaesth 1990;64: 563–70.

    Google Scholar 

  44. O'Kelly B, Jayais P, Veroli P, Lhuissier C, Ecoffey C. Dose requirements of vecuronium, pancuronium, and atracurium during orthotopic liver transplantation. Anesth Analg 1991;73:794–8.

  45. Kisor DF, Schmith VD, Wargin WA, Lien CA, Ornstein E, Cook DR. Importance of organ independent elimination of cisatracurium. Anesth Analg 1996;83:1065–71.

    Google Scholar 

  46. Klaassen CD, Watkins III JB. Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol Rev 1984;36:1–67.

    Google Scholar 

  47. Mortimer PR, Mackie DB, Haynes S. Ampicillin levels in human bile in the presence of biliary tract disease. Br Med J1969;3:88–9.

    Google Scholar 

  48. Sales JEL, Sutcliffe M, O'Grady F. Cephalexin levels in human bile in the presence of biliary tract disease. Br Med J 1972;3:441–2.

    Google Scholar 

  49. Brown RB, Martyak SN, Barza M, Curtis L, Weinstein L. Penetration of clindamycin phosphate into the abnormal human biliary tract. Ann Intern Med 1976;84:168–70.

    Google Scholar 

  50. Drew R, Priestley BG, O'Reilly WJ. Hexobarbital pharmacokinetics in rats after ligation of the common bile duct. J Pharmacol Exp Ther1977;201:534–40.

    Google Scholar 

  51. Saudek F, Moravek J, Modr Z. Cefoperazone pharmacokinetics in patients with liver cirrhosis: a predictive value of the ujoviridin test. Int J Clin Pharmacol Ther Toxicol 1989;27:82–7.

    Google Scholar 

  52. Krakamp B, Tanswell P, Leidig P, Vogel H, Schmitz R, Bozler G. Steady state intravenous pharmacokinetics of pirenzepine in patients with hepatic insufficiency. Eur J Clin Pharmacol 1989;36:71–3.

    Google Scholar 

  53. Gonzales G, Aransibia A, Rivas MI, Caro P, Antezana C. Pharmacokinetics of frusemide in patients with hepatic cirrhosis. Eur J Clin Pharmacol 1982;22:315–20.

    Google Scholar 

  54. Marcantonio LA, Auls WHR, Murdoch WR, Purohit R, Skellern GG, Howes CA. The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. Br J Clin Pharmacol 1983;25:245–52.

    Google Scholar 

  55. Cello JP, Oie S. Cimetidine disposition in patients with Laennec's cirrhosis during multiple dosing therapy. Eur J Clin Pharmacol 1983;25:223–9.

    Google Scholar 

  56. Smith IL, Ziemniak JA, Bernhard H, Eshelman FN, Martin LE, Schentag JJ. Ranitidine disposition and systemic availability in hepatic cirrhosis. Clin Pharmacol Ther 1984;35:487–94.

    Google Scholar 

  57. Papadakis MA, Arieff AI. Progressive deterioration of renal function in non-azotemic cirrhotic patients with ascites: a prospective study. Kidney Internat 1985;27:149.

    Google Scholar 

  58. Papadakis MA, Arieff AI. Unpredictability of clinical evaluation of renal function in cirrhosis. Am J Med 1987;82:945–52

    Google Scholar 

  59. Granneman GR, Mahr G, Locke C, Nickel P, Kirch W, Fabian W, Kinzig M, Naber KG, Sörgel F. Pharmacokinetics of temafloxacin in patients with liver impairment. Clin Pharmacokinet (Suppl 1) 1992;22:24–32.

    Google Scholar 

  60. Caregaro L, Menon F, Angeli P, Amodio P, Merkel C, Bortoluzzi A, Alberino F, Gatta A. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994;154:201–5.

    Google Scholar 

  61. Caujolle B, Ballet F, Poupon R. Relationships among betaadrenergic blockade, propranolol concentration, and liver function in patients with cirrhosis. Scand J Gastroenterol 1988;23:925–30.

    Google Scholar 

  62. Ramond MJ, Comoy E, Lebrec D. Alterations in isoprenaline sensitivity in patients with cirrhosis: evidence of abnormality of the sympathetic nervous activity. Br J Clin Pharmacol 1986;21:191–6.

    Google Scholar 

  63. Gerbes AL, Remien J, Jungst D, Sauerbruch Y, Paumgartner G. Evidence for down-regulation of beta-2-adrenoreceptors in cirrhosis patients with severe cirrhosis. Lancet 1986;1: 1409–11.

    Google Scholar 

  64. Janku I, Perlik F, Tkaczykova M, Brodanova M. Disposition kinetics and concentration-effect relationship of metipranolol in patients with cirrhosis and healthy subjects. Eur J Clin Pharmacol 1992;42:337–40.

    Google Scholar 

  65. Keller E, Hoppe-Seyler G, Mumm R, Schollmeyer P. Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide. Eur J Clin Pharmacol 1981;20:27–33.

    Google Scholar 

  66. Villeneuve JP, Verbeeck RK, Wilkinson GR, Branch RA. Furosemide kinetics and dynamics in cirrhosis. Clin Pharmacol Ther 1986;40:14–20.

    Google Scholar 

  67. Dao MT. Villeneuve JP. Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis. Clin Invest Med 1988;11:6–9.

    Google Scholar 

  68. Villeneuve JP, Rocheleau F, Raymond G. Triamterene kinetics and dynamics in cirrhosis. Clin Pharmacol Ther 1984;35:831–7.

    Google Scholar 

  69. Schwartz S, Brater DC, Pound D, Green PK, Kramer WG, Rudy D. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide in patients with cirrhosis. Clin Pharmacol Ther 1993;54:90–7.

    Google Scholar 

  70. Gentilini P, La Villa G, Marra F, Carloni V, Melani L, Foschi M, Cotrozzi G, Quartini M, Chibbaro G, Tommassi AC, Bernareggi A, Simoni A, Buzzelli G, Laffi G. Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites. J Hepatol 1996;25:481–90.

    Google Scholar 

  71. Marcantonio LA, Auld WHR, Murdoch WR, Purohit R, Skellern GG, Howes CA. The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.Br J Clin Pharmacol 1983;15:245–52.

    Google Scholar 

  72. Bakti G, Fisch HU, Karlaganis G, Minder C, Bircher J. Mechanism of the excessive sedative response of cirrhotics to benzodiazepines: model experiments with triazolam. Hepatology 1987;7:629–38.

    Google Scholar 

  73. MacGilchrist AJ, Birnie GG, Cook A, Scobie G, Murray T, Watkinson G, Brodie MJ. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut 1986;27:190–5.

    Google Scholar 

  74. Kimelblatt BJ, Cerra FB, Calleri G, Berg MJ, McMillen MA, Schentag JJ. Dose and serum concentration relationships in cimetidine-associated mental confusion. Gastroenterology 1980;78:791–5.

    Google Scholar 

  75. Schentag JJ, Cerra FB, Calleri G, Leising ME, French MA, Bernhard H. Age, disease and cimetidine disposition in healthy subjects and chronically ill patients. Clin Pharmacol Ther 1981;29:737–43.

    Google Scholar 

  76. Shafer DF, Fowler VM, Munson PJ, Thakur AK, Waggoner JG, Jones EA. Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure. J Lab Clin Med 1983;102:870–80.

    Google Scholar 

  77. Zeneroli ML. Hepatic encephalopathy. Experimental studies in a rat model of fulminant hepatic failure. J Hepatol 1985;1: 301–12.

    Google Scholar 

  78. Ferenci P, Shafer DF, Kleinberger G, Hoofnagle JH, Jones EA. Serum levels of gamma-aminobutyric acid-like activity in acute and chronic hepatocellular disease. Lancet1983;2:811–4.

    Google Scholar 

  79. Butterworth RF, Lavoie J, Giguere JF, Pomier-Layrargues G. Affinities and densities of high affinity [3H] muscimol (GABAA) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Hepatology 1988;8:1084–8.

    Google Scholar 

  80. Maddison JE, Dodd PR, Johnston GAR, Farrell GC. Brain gamma-aminobutyric acid receptor binding is normal in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma gamma-aminobutyric acid-like activity. Gastroenterology 1987;93:1062–8.

    Google Scholar 

  81. Groeneweg M, Gyr K, Amrein R, Scollo-Lavizzari G, Williams R, Yoo JY, Schalm SW. Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial. Electroencephalogr Clin Neurophysiol 1996;98:29–34.

    Google Scholar 

  82. Pomier-Layrargues G, Giguere JF, Lavoie J, Perney P, Gagnon S, D'Amour M, Wells J, Butterworth RF: Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial. Hepatology 1994;9;32–7.

    Google Scholar 

  83. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices.Br J Surg 1973;60:646–9.

    Google Scholar 

  84. Brockmöller J, Roots I. Assessment of liver metabolic function. Clinical implications. Clin Pharmacokinet 1994;27:216–48.

    Google Scholar 

  85. Jalan R, Hayes PC. Review article: quantitative tests of liver function. Aliment Pharmacol Ther 1995;9:263–70.

    Google Scholar 

  86. Soons PA, De Boer A, Cohen AF, Breimer DD. Assessment of hepatic blood flow in healthy subjects by continuous infusion of indocyanine green. Br J Clin Pharmacol 1991;32:697–704.

    Google Scholar 

  87. Keiding S. Hepatic clearance and liver blood flow. J Hepatol 1987;4:393–8.

    Google Scholar 

  88. Zeeh J, Lange H, Bosch J, Pohl S, Loesgen H, Eggers R, Navasa M, Chesta J, Bircher J. Steady-state extrarenal sorbitol clearance as a measure of hepatic plasma flow. Gastroenterol 1988;95:749–59.

    Google Scholar 

  89. Oellerich M, Burdelski M, Lautz H-U, Schulz M, Schmid FW, Herrmann H. Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis. Ther Drug Monit 1990;12:219–26.

    Google Scholar 

  90. Horsmans Y, Desager JP, Daenens C, Harvengt C, Geubel AP.D-Propoxyphene and norpropoxyphene kinetics after the oral administration of D-propoxyphene: a new approach to liver function? J Hepatol 1994;21:283–91.

    Google Scholar 

  91. Watkins PB, Hamilton TA, Annesley TM, Ellis CN, Kolars JC, Voorhees JJ. The erythromycin breath test as a predictor of cyclosporine blood levels. Clin Pharmacol Ther 1990;48: 120–9.

    Google Scholar 

  92. Fabre D, Bressolle F, Gomeni R, Bouvet O, Dubois A, Raffanel C, Gris JC, Galtier M. Identification of patients with impaired hepatic drug metabolism using a limited sampling procedure for estimation of phenazone (antipyrine) pharmacokinetic parameters. Clin Pharmacokinet 1993;24:333–43.

    Google Scholar 

  93. Pauwels S, Geubel AP, Dive C, Beckers C. Breath 14CO2 after intravenous administration of 14C aminopyrine in liver diseases. Dig Dis Sci 1982;27:49–56.

    Google Scholar 

  94. Renner E, Wietholtz H, Huguenin P, Arnaud MJ, Preisig R. Caffeine: a model compound for measuring liver function. Hepatology 1984;4:38–46.

    Google Scholar 

  95. Huet PM, Villeneuve JP. Determinants of drug disposition in patients with cirrhosis. Hepatology 1983;3:913–918; Branch RA Drugs as indicators of hepatic function. Hepatology 1982;2: 97-105.

    Google Scholar 

  96. Shand DG, Kornhauser DM, Wilkinson GR. Effect of route of administration and blood flow on hepatic drug elimination.J Pharmacol Exp Ther 1975;195:416–23.

    Google Scholar 

  97. Morgan DJ, Smallwood RA. Clinical significance of pharmacokinetic models of hepatic elimination. Clin Pharmacokinet 1990;18:6176.

    Google Scholar 

  98. Meyer-Wyss B, Renner E, Luo H, Scholer A. Assessment of lidocaine metabolite function in comparison with other quantitative liver function tests. J Hepatol 1993;19:133–9.

    Google Scholar 

  99. Kawasaki S, Immamura H, Bandai Y, Sanjo K, Idezuki Y. Direct evidence for the intact hepatocyte theory in patients with liver cirrhosis. Gastroenterology1992;102:1351–5.

    Google Scholar 

  100. Colli A, Buccino G, Cocciolo M, Parravicini R, Scaltrini G.Disposition of a flow-limited drug (lidocaine) and a metaboliccapacity limited drug (theophylline) in liver cirrhosis. Clin Pharmacol Ther 1988;44:642–9.

    Google Scholar 

  101. Breimer DD, Schellens JHM. A 'cocktail' strategy to assess the in vivo oxidative drug metabolism in humans. Trends in Pharmacol Sci 1990;11:223–5.

    Google Scholar 

  102. Gill MA, Kern JW. Altered gentamicin distribution in ascitic patients.Am J Hosp Pharm 1979;36:1704–6.

    Google Scholar 

  103. Branch RA, James J, Read AE. A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)-propranolol. Br J Clin Pharmacol 1976;3:243–9.

    Google Scholar 

  104. Hebert MF. Guide to drug dosage in hepatic disease. In Avery's Drug Treatment, edited by TM Speight and NHG Holford, ADIS International Ltd., Auckland, 1997:161–92.

    Google Scholar 

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  1. ucl/fatc 7355, School of Pharmacy, Av. E. Mounier 73, 1200, Brussels, Belgium

    R.K. Verbeeck

  2. Department of Gastroenterology, Catholic University of Louvain, Brussels, Belgium

    Y. Horsmans

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Verbeeck, R., Horsmans, Y. Effect of hepatic insufficiency on pharmacokinetics and drug dosing. Pharm World Sci 20, 183–192 (1998). https://doi.org/10.1023/A:1008656930082

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