Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: article review
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
review article or handbook
Title:
Clinical pharmacokinetics of therapeutic bile acids
Author:
Crosignani A, Setchell KD, Invernizzi P, Larghi A, Rodrigues CM and Podda M.
Year:
1996
Bibliographic source:
Clinical Pharmacokinetis, 30(5), 333-58

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
The article is a review of the toxicokinetics of ursodeoxycholic acid.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Ursodeoxycholic acid is not well absorbed by the gastrointestinal tract.
Details on distribution in tissues:
It is efficiently extracted by the liver, where it is conjugated with glycerine and taurine and then secreted in the bile. Afterwards it undergo into the enterohepatic circulation together with the other bile salts.
Details on excretion:
The elimination of ursodeoxycholic acid, unmodified or after bacterial biotrasformation to lithocholic acid, occurs mainly by feces.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Intestinal bacteria biodegrade ursodeoxycholic acid to lithocholic acid.

Bioaccessibility

Bioaccessibility testing results:
The clearance of urodeoxycholic acid is low because it enters the enterohepatic recirculation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Ursodeoxycholic acid is not well absorbed by the gastrointestinal tract but, if absorbed, its clearance is low because it enters the enterohepatic recirculation. Serum concentration of ursodeoxycholic acid is low, therefore it is not extensively distributed.
Executive summary:

This article reviewed the pharmacokinetics of chenodeoycholic acid and of ursodeoxycholic acid. Ursodeoxycholic acid is not well absorbed by the gastrointestinal tract. It is efficiently extracted by the liver, where it is conjugated with glycerine and taurine and then secreted in the bile. Afterwards it undergo into the enterohepatic circulation (resulting in low serum concentrations) together with the other bile salts and, despite the rapid hepatic extraction, the clearance of the substance is low because of the enterohepatic recirculation. The elimination of ursodeoxycholic acid, unmodified or after bacterial biotrasformation to lithocholic acid, occurs mainly by feces.