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Abstract

Localization of glutathione conjugation activities toward bromosulfophthalein in perfused rat liver. Studies with the multiple indicator dilution technique.

Y Zhao, C A Snel, G J Mulder and K S Pang
Drug Metabolism and Disposition November 1993, 21 (6) 1070-1078;
Y Zhao
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C A Snel
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G J Mulder
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K S Pang
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Abstract

The plasma binding and conjugation kinetics of bromosulfophthalein (BSP) with glutathione (GSH) were studied in the single-pass in situ perfused rat liver (portal vein perfusion at 10 ml/min); GSH in postmitochondrial fractions of the liver at the end of the experiment was examined as a potential rate-determining factor. BSP was highly bound to 1% albumin with at least two classes of binding sites: one of 0.17 site with an association constant of 1.9 x 10(7) M-1, and one of 7.4 equivalent sites of association constant, 1.3 x 10(5) M-1. Nonlinear binding was observed within between 5-1500 microM BSP. At varying input concentrations (0.4-250 microM) of BSP, the unbound fraction was extremely low (< 0.005) and the hepatic extraction ratio declined from 0.67 to 0.15; loss of BSP was primarily caused by GSH conjugation to form BSP-GSH, which appeared exclusively in bile. Additionally, unchanged BSP and two very minor unidentified metabolites were also excreted in bile. The formation of BSP-GSH proceeded with an apparent Vmax of 22 nmol/min/g and a KM of 0.05 microM, whereas the parameters for BSP excretion were 0.85 nmol/min/g and 0.02 microM, respectively. Within the concentration range of BSP examined, GSH availability did not appear to be rate-limiting in the formation or excretion of BSP-GSH.(ABSTRACT TRUNCATED AT 250 WORDS)

 

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Drug Metabolism and Disposition
Vol. 21, Issue 6
1 Nov 1993
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Abstract

Localization of glutathione conjugation activities toward bromosulfophthalein in perfused rat liver. Studies with the multiple indicator dilution technique.

Y Zhao, C A Snel, G J Mulder and K S Pang
Drug Metabolism and Disposition November 1, 1993, 21 (6) 1070-1078;

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Abstract

Localization of glutathione conjugation activities toward bromosulfophthalein in perfused rat liver. Studies with the multiple indicator dilution technique.

Y Zhao, C A Snel, G J Mulder and K S Pang
Drug Metabolism and Disposition November 1, 1993, 21 (6) 1070-1078;
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