English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

By means of the multiple indicator dilution (MID) method, the sequestration process of 4-methylumbelliferone (4-MU), which is well known to be conjugated to glucuronide (4-MUG) and sulfate (4-MUS) in the rat liver, was found to be saturated as the dose was increased J. Pharmacokin. Biopharm., 15, 25 (1987). This observation might be attributed to the saturation of the conjugative metabolism. In the present study, using an in vivo tissue sampling single injection technique, we determined whether the sequestration process obtained by means of the MID method reflected the conjugative metabolism process. When the dose of 4-MU was increased from a low dose (110μg/rat) to a high dose (3200 μg/rat), FDapp, 4-MUS and FDapp, 4-MUG, which represent the fractions of the amounts of the formed 4-MUG and 4-MUS remaining in the liver, respectively, remarkably decreased. Since 4-MUG and 4-MUS formed from 4-MU have low diffusional clearances between the blood and hepatocytes, they are effectively trapped in the hepatocytes and therefore FDapp, 4-MUS and FDapp, 4-MUG represent the extents of the conjugative metabolism of 4-MU. Therefore, the dose-dependent change in the sequestration process was found to be attributable to the saturation of the conjugative metabolism. This observation confirms our previous hypothesis that the saturation of the sequestration process observed by using the MID method reflected that of the conjugative metabolism. Furthermore, according to the “sinusoidal” model, we simulated the time profiles of the amounts of drugs remaining in the liver, using parameters obtained from the MID data. The model, which has 20 sinusoidal compartments and can be regarded as identical to a “parallel tube” model, could reliably predict the time profiles of the amounts of drugs remaining in the liver.

chemical and pharmaceutical bulletin/chemical and pharmaceutical bulletin

Conjugative metabolism of 4-methylumbelliferone in the rat liver: Verification of the sequestration process in multiple indicator dilution experiments.