Summary
The metabolism of indocyanine green, bromsulphophthalein and bilirubin was studied before and after a treatment for 2 weeks with cimetidine 1.0 g/day in 12 subjects with Gilbert's syndrome. There was no effect on the plasma clearance of indocyanine green and bromsulphophthalein, on the maximal biliary excretion capacity of bromsulphophthalein, on serum bilirubin concentrations or on the biliary metabolites of bromsulphophthalein and bilirubin. It is concluded that in Gilbert's syndrome two weeks of treatment with cimetidine had no effect on liver blood flow or on conjugation mechanisms which were independent of cytochrome P450.
Similar content being viewed by others
References
Jones RH, Rudge CJ, Bewick M, Parsons V, Weston MJ (1978) Cimetidine: prophylaxis against upper gastrointestinal hemorrhage after renal transplantation. Br Med J 1: 398–400
Brimblecombe RW, Duncan WAM, Durant GJ, Emmett JC, Ganellin CR, Parsons ME (1975) Cimetidine — a nonthiourea H2-receptor antagonist. J Int Med Res 3: 86–92
Serlin MJ, Challiner M, Park BK, Turcan PA, Breckenridge AN (1980) Cimetidine potentiates the anticoagulant effect of warfarin by inhibition of drug metabolism. Biochem Pharmacol 29: 1971–1972
Desmond PV, Patwardhan R, Parker R, Schenker S, Speeg KV Jr (1980) Effect of cimetidine and other antihistaminics on the elimination of aminopyrin, phenacetin and caffein. Life Sci 26: 1261–1268
Klotz U, Antilla VJ, Reimann J (1979) Cimetidine/diazepam interaction (letter). Lancet 2: 699
Bircher J, Küpfer A, Gikalov I, Preisig R (1976) Aminopyrine demethylation measured by breath analysis in health and in cirrhosis of the liver. Clin Pharmacol Ther 20: 484–492
Schillings RT, Schrader SR, Ruelins HW (1971) Urinary metabolites of lorazepam in humans and four animals species. Arzneimittelforsch 21: 1059–1065
Johnson RF, Schenker S, Roberts RK (1979) Plasma binding of benzodiazepines in humans. J Pharm Sci 68: 1320–1322
Patwardhan RV, Yarborough GW, Desmond PV, Johnson RF, Schenker S, Speeg KV Jr (1980) Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology 79: 912–916
Feely J, Wilkinson GR, Wood AJJ (1981) Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 304: 692–695
Garg DC, Weidler DJ, Jallad NS, Eshelman FN (1982) The effect of ranitidine and cimetidine on hepatic blood flow (abstract). Clin Pharmacol Ther 31: 228
Lebrec D, Goldfarb G, Benhamou JP (1981) Reduction in liver blood flow by cimetidine (letter). N Engl J Med 305: 100
Berk PD, Bloomer JR, Howe RB, Berlin NI (1970) Constitutional hepatic dysfunction (Gilbert's syndrome). A new definition based on kinetic studies with unconjugated radio bilirubin. Amer J Med 49: 296–305
Black M, Billing BH (1969) Hepatic bilirubin UDP-glucuronyl transferase activity in liver disease and Gilbert's syndrome. N Engl J Med 280: 1266–1271
Berk PD, Blaschke TF, Waggoner JG (1972) Defective bromsulphthalein clearance in patients with constitutional hepatic dysfunction (Gilbert's syndrome). Gastroenterology 63: 472–481
Martin JF, Vierling JM, Wolkoff AW, Scharschmidt BF, Vergalla J, Wagoner JG, Berg PD (1976) Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology 70: 385–391
Ohkubo H, Okuda K, Jida S (1981) A constitutional unconjugated hyperbilirubinaemia combined with indocyanine green intolerance: a new functional disorder? Hepatology 1: 319–324
Fevery J, Verwilghen R, Than TG, De Groote J (1979) Glucuronidation of bilirubin and the occurence of pigment gall stones in patients with chronic haemolytic diseases. Eur J Clin Invest 10: 219–226
Preisig R, Williams R, Sweeting J, Bradley SE (1966) Changes in sulphobromphtalein transport and storage by the liver during viral hepatitis in man. Amer J Med 40: 170–183
Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S (1961) The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci Mol Med 21: 43–57
Michaelsson M, Nosslin B, Sjölin S (1965) Plasma bilirubin determination in the newborn infant. A methodological study with special reference to the influence of hemolysis. Pediatrics 35: 925–931
Van Roy FP, Heirwegh KPM (1968) Determination of bilirubin glucuronyl transferase with bilirubin as acceptor. Biochem J 107: 507–518
Kutz K, Kandler H, Gugler R, Fevery J (1984) Effect of clofibrate on the metabolism of bilirubin, bromsulphthalein and indocyanine green and on biliary lipid composition in Gilbert's syndrome. Clin Sci 66: 389–397
Paumgartner G, Horak W, Probst P, Grabner G (1971) Effect of phenobarbital on bile flow and bile salt excretion in the rat. Nauny-Schmiedebergs Arch Pharmacol 270: 98–101
Abell LL, Levy BB, Brodie BB, Kendall FE (1952) A simplified method for the estimation of total cholesterol in serum and demonstration of its specifity. J Biol Chem 195: 357–366
Bartlett GR (1950) Phosphorus assay in column chromatographie. J Biol Chem 234: 466–468
Thomas WJ, Hofmann AF (1973) A simple calculation of the lithogenic index of bile: expressing biliary lipid composition on rectangular coordinates. Gastroenterology 65: 698–700
Quarfordt SH, Hildermann HL, Valle T, Ladell E (1971) Compart mental analysis of BSP-transport in normal patients and patients with hepatic dysfunction. Gastroenterology 60: 246–255
Häcki W, Bircher J, Preisig R (1976) A new look at the plasma disappearance of sulphobromophthalein (BSP): correlation with the BSP-transport maximum and the hepatic plasma flow in man. J Lab Clin Med 88: 1019–1031
Lienert GA (1973) Verteilungsfreie Methode in der Biostatistik, 2nd edn. H. Hain, Meisenheim am Glar, FRG
Scharschmidt B, Gollan JL (1979) Current concepts of bilirubin metabolism and hereditary hyperbilirubinemia. Edited by Popper H, Schaffner F (ed) Progress in liver diseases, vol 6. Grune and Stratton, New York, pp 187–211
Leevy CM, Bender J, Silverberg M, Neylor J (1963) Physiology of dye extraction by the liver: comparative studies of sulphobromphthalein and indocyanine green. An NY Acd Sci 111: 161–175
Fevery J, Blankaert N, Heirwegh KPM, Preaux AM, Berthelot P (1977) Unconjugated bilirubin and an increased proportion of bilirubin monoconjugates in the bile of patients with Gilbert's syndrome and Crigler-Najjar disease. J Clin Invest 60: 970–979
Daneshmend TK, Ene MD, Parker G, Roberts CJC (1984) Effects of chronical oral cometidine on apparent liver blood flow and hepatic microsomal enzyme activity in man. Gut 25: 125–128
Reyes H, Levy AJ, Gatmaitan C, Arias M (1971) Studies of Y and Z, two hepatic cytoplasmatic organic anion-binding proteins: effect of drugs, chemicals, hormones and cholestases. J Clin Invest 50: 2242–2252
Author information
Authors and Affiliations
Additional information
The work forms part of a thesis for MD degree of M.D., University of Bonn, FRG
Rights and permissions
About this article
Cite this article
Kutz, K., Deres, M. Effect of cimetidine on the metabolism of cholephilic dyes in Gilbert's syndrome. Eur J Clin Pharmacol 27, 227–232 (1984). https://doi.org/10.1007/BF00544050
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00544050