Abstract
The fact that the role of conjugation cannot be neglected in the definition and evaluation of the different maximal transfer rates introduced in the literature (Tm, Lm) is demonstrated. Free and conjugated BSP were measured both in blood and bile during constant infusion of free BSP in man. These data proved very useful to develop a careful model of BSP metabolism able to interpret all major known facts in saturation conditions. The model shows that, in the conditions used for the Wheelter-test, biliary excretion is saturated both for free and conjugated BSP. At higher infusion rates, there is also saturation of the hepatic uptake of conjugated BSP. No other processes are saturated in these conditions. Lastly, free and conjugated BSP are excreted at a maximal rate that is not dependent on their respective amounts in the liver; this suggests the existence of independent transport mechanism in biliary excretion for free and conjugated BSP during the infusion of free BSP.
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Clarkson, M. J., Hall, S. E. andRiachards, T. G. (1970). The measurement of the storage capacity, or relative volume, of the liver by the single intravenous injection of bromsulphthalein in the turkey.Res. Vet. Sci.,11, 37–44.
Giangrandi, E., Ghemi, F., Molino, G. P., Crevario, A. Brusa, L. andDefilippi, P. (1966) Il flusso epatico nel soggetto normale stimato con l'uso di Au198 e della clearance di piccole dosi di bromosulfonftaleina.Arch. It. Mal. App. Digerente.,33, 429–434.
Goodman, R. D. (1952) Bromsulfalein clearance a quantitative clinical test of liver function.J. Lab. Clin. Med.,40, 531–536.
Hachi, W., Bircher, J. andPreisig, R. (1976) A new look at the plasma disappearance of sulfobromophthalein (BSP): correlation with the BSP transport maximum and the hepatic plasma flow in man.J. Lab. Clin. Med.,88, 1019–1031.
Mason, M., Hawley, G. andSmith, A. (1948) Application of the saturation principle to the estimation of functional hepatic man in normal dogs.Amer. J. Physiol.,42, 42–47.
McIntyre, N., Mulligan, R. andCarson, E. (1973) BSP-Tm andS. A critical re-evaluation. In:The liver quantitative aspects of structure and function. Karger, Basel, 417–427.
Meitzer, J., Wheeler, H. O. andCranston, W. I. (1959) Metabolism of sulfobromophthalein in radium (BSP) in dog and man.Proc. Soc. Exp. Biol. (NY),100, 174.
Milanese, M., Molino, G. andVilla, A. (1976) Pathophysiological information on hepatic functions from standard measurements of the kinetics of BSP. IV IFAC Symposium on System Identification and Parameter Estimation, Tbilisi, 448–458.
Milanese, M. andVilla, A. (1976) A critical analysis of saturation phenomena in hepatic kinetics of drugs. 3rd European Meeting on Cybernetics and System Research, Vienna.
Molino, G. andMilanese, M. (1975) Structural analysis of compartmental models for the hepatic kinetics of drugs.J. Lab. Clin. Med.,85, 865–878.
Pagliardi, E., Giangrandi, E. andMolino, G. (1963) Studies on the maximal hepatic sulfobromophthalein removal rate.Am. J. Dig. Diseases,8, 251–266.
Philip, J. R., Grodsky, G. M. andCarbone, J. V. (1961) Mercaptide conjugation in the uptake and secretion of sulfobromophthalein.Am. J. Physiol.200, 545–547.
Schoenfield, L., McGill, D. B. andFoulk, W. T. (1964). Studies of sulfobromophthalein sodium (BSP) metabolism in man. III, Demonstration of a transport maximum (Tm) for biliary excretion of BSP.J. Clin. Invest.,43, 1424–1432.
Segre, G. (1972) Kinetics of drugs in the hepatobiliary system. InLiver and drugs,Orlandi,F. andJezequel,A. M. (Eds.), Academic Press, New York, 85–105.
Skaunic, V., Nerad, V. andFendrichova, M. (1970) Mechanismus poklesu relativni stradaci schopnosti jater pro bromsulfalein S rostoucim vekem. II Vyznam snizeneho jaterniho protoku krve.Cs. Gastroent. Vyz,24, 206–215.
Taleisnik, S. (1955) Liver mass determination by bromosulphalein in partially hepatectomized rabbits.Gastroenterology,29, 64–71.
Verschure, J. C. M. (1952) Clinical use of measurements of clearance and maximum capacity of the liver.Acta Med. Scand.,142, 409–419.
Wheeler, H. O., Meltzer, J. J. andBradly, S. E. (1960) Biliary transport and hepatic storage of sulfobromophthalein sodium in the unanesthetized dog, in normal man and in patients with hepatic diseases.J. Clin. Invest.,39, 1131–1143.
Whelan, G. andCombes, B. (1971) Competition by unconjugated and conjugated BSP for transport into bile. Evidence for a single excretory system.J. Lab. Clin. Med.,78, 231–244.
Whelan, G., Hock, J. andCombes, B. (1970) A direct assessment of the importance of conjugation for biliary transport of sulfobromophthalein sodium.J. Lab. Clin. Med.,75, 542–557.
Wilkinson, P., O'Day, D. M., Breen, K. J. andRankin, J. G. (1968) Bromosulphthalein metabolism in acute alcoholic liver disease.Gut,9, 707–711.
Winkler, K. andGram, C. (1965) The kinetics of bromsulphthalein elimination during continuous infusion in man.Acta Med. Scand.,178, 439–452.
Winkler, K., Keiding, S. andTygstrup, N. (1973) Clearance as a quantiative measure of liver function. InThe liver quantitative aspects of structure and function, First International Gstaad Symposium. Karger, Basel, 144–155.
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Milanese, M., Molino, G. & Cappelletti, F. New results on saturation phenomena in BSP metabolism: the role of free and conjugated BSP. Med. Biol. Eng. Comput. 19, 707–716 (1981). https://doi.org/10.1007/BF02441332
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DOI: https://doi.org/10.1007/BF02441332