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Computer simulation of sulfobromophthalein kinetics in the rat using flow-limited models with extrapolation to man

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Abstract

A linear, flow-limited mathematical model of drug kinetics was used to simulate total sulfobromophthalein (BSP) kinetics in normal anesthetized rats during intravenous infusions and following rapid intravenous injections. Four parameters were used to characterize the distribution and biliary and urinary excretion of BSP: liver- to- plasma concentration ratio, extrahepatic tissue- to- plasma concentration ratio, liver clearance rate constant, and renal plasma clearance rate constant. The same parameters appear to characterize the kinetics of BSP in man through the successful application of “scale- up” techniques utilizing data from experiments in rats. Plasma levels of BSP corresponding to intravenous infusions and rapid intravenous injections in man are approximated by computer simulation.

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Abbreviations

C p :

BSP concentration in plasma

C l :

BSP concentration in liver

C bi :

BSP concentration in bile compartmenti, i = 1,2,3

C m :

BSP concentration in extrahepatic tissue

V p :

volume of plasma

V l :

volume of liver

V b :

volume of bile

V m :

volume of extrahepatic tissue

Q l :

plasma flow rate through liver

Q m :

plasma flow rate through extrahepatic tissue

Q b :

bile flow rate through biliary tract

R l :

hepatic tissue-to-hepatic venous plasma concentration ratio of BSP

R m :

extrahepatic tissue-to-extrahepatic venous plasma concentration ratio of BSP

k l :

hepatic tissue elimination rate constant for BSP

k k :

renal plasma clearance rate constant for BSP

f(t) :

infusion rate function

f i :

volume of bile in the bile duct compartment as a fraction of the total bile volume Vb

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Authors and Affiliations

  1. The Toxicology Center, Department of Pharmacology and Department of Pediatrics, University of Iowa, School of Medicine, 52242, Iowa City, Iowa

    B. Montandon, R. J. Roberts & L. J. Fischer

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  1. B. Montandon
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  2. R. J. Roberts
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  3. L. J. Fischer
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Montandon, B., Roberts, R.J. & Fischer, L.J. Computer simulation of sulfobromophthalein kinetics in the rat using flow-limited models with extrapolation to man. Journal of Pharmacokinetics and Biopharmaceutics 3, 277–290 (1975). https://doi.org/10.1007/BF01066923

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  • DOI: https://doi.org/10.1007/BF01066923

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