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Toxicological information

Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from peer-reviewed handbook.

Data source

Reference
Reference Type:
review article or handbook
Title:
Pharmacokinetics and metabolism of the salicylates
Author:
Graham GG, Roberts MS, Day RO, Rainsford KD
Year:
2004
Bibliographic source:
In: Aspirin and Related Drugs, Ed Rainsford KD, Taylor & Francis, London p.97-155

Materials and methods

Type of study / information:
Metabolic profile for ASA and other salicylates
Endpoint addressed:
basic toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Review of published data

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Results:
The major metabolic pathway for elimination of salicylate is via conjugation. The principal metabolite in humans is salicyluric acid. A minor oxidative pathway leads to production of 2,5-dihydroxybenzoic acid (gentisic acid, 25DHBA) and 2,3-dihydroxybenzoic acid.

Any other information on results incl. tables

The major metabolic pathway for elimination of salicylate is via conjugation. The principal metabolite in humans is salicyluric acid (SUA) produced by conjugation with glycine. Synthesis of salicylurate is saturable, reducing from 80 to 85% of daily dose as ASA dose increases from 1 to 4g per day. Conjugation with glucuronic acid forms salicylic acid phenolic glucuronide (SAPG) and/or salicylic acid acyl glucuronide (SAAG) accounting for about 20 and 10% of administered dose respectively. A minor oxidative pathway leads to production of 2,5-dihydroxybenzoic acid (gentisic acid, 25DHBA), accounting for less than 5% of elimination of drug dose and lower concentrations of 2,3-dihydroxybenzoic acid (23DHBA). Gentisic acid may be conjugated with glucuronic acid to produce gentisic acid phenolic glucuronide.

Applicant's summary and conclusion

Conclusions:
The major metabolic pathway for elimination of ASA and its hydrolysis product salicylate is via conjugation. The principal metabolite in humans is salicyluric acid.
Executive summary:

The metablic profile of ASA was reviewed (Graham, 2004). The major metabolic pathway for elimination of salicylate is via conjugation. The principal metabolite in humans is salicyluric acid (SUA) produced by conjugation with glycine. Synthesis of salicylurate is saturable, reducing from 80 to 85% of daily dose as ASA dose increases from 1 to 4g per day. Conjugation with glucuronic acid forms salicylic acid phenolic glucuronide (SAPG) and/or salicylic acid acyl glucuronide (SAAG) accounting for about 20 and 10% of administered dose respectively. A minor oxidative pathway leads to production of 2,5-dihydroxybenzoic acid (gentisic acid, 25DHBA), accounting for less than 5% of elimination of drug dose and lower concentrations of 2,3-dihydroxybenzoic acid (23DHBA). Gentisic acid may be conjugated with glucuronic acid to produce gentisic acid phenolic glucuronide