Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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

Test material information

Constituent 1

Reference substance name:

Ursodeoxycholic acid

EC Number:

204-879-3

EC Name:

Ursodeoxycholic acid

Cas Number:

128-13-2

IUPAC Name:

3,7-dihydroxycholan-24-oic acid

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 (or Bioavailability)

Bioaccessibility (or Bioavailability) 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.