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Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Adequacy of study:
other information

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The metabolism of dibenzylamine: identification of N,N-dibenzylhydroxylamine as the major in vitro metabolic procuct from rabbit fortified hepatic homogenates.
Author:
Beckett AH, Coutts RT, Gibson GG
Year:
1975
Bibliographic source:
J Pharm Pharmacol 7727, 659-665
Reference Type:
publication
Title:
Microsomal N-hydroxylation of dibenzylamine
Author:
Beckett AH, Gibson GG
Year:
1975
Bibliographic source:
Xenobiotical 5, 677-686

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Homogenized male rabbit liver 9000g supernatant was incubated with N,N-Dbenzylamine under aerobic conditions for 60 minutes.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibenzylamine
EC Number:
203-117-7
EC Name:
Dibenzylamine
Cas Number:
103-49-1
Molecular formula:
C14H15N
IUPAC Name:
dibenzylamine
Details on test material:
purity: laboratory reagent grade ( no further detail)
Radiolabelling:
no

Test animals

Species:
other: rabbit liver
Strain:
New Zealand White
Sex:
male

Administration / exposure

Route of administration:
other: isolated rat liver 9000 g supenatant was treated
Vehicle:
water
Duration and frequency of treatment / exposure:
once 60 min
Doses / concentrations
Remarks:
Doses / Concentrations:
10 µmol
No. of animals per sex per dose / concentration:
in vitro investigation
Control animals:
other: control incubations (1) rabbit liver homogenate without substate

Results and discussion

Main ADME resultsopen allclose all
Type:
metabolism
Results:
The study has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized , 90 % is converted to N,N-dibenzylhydroxylamine. The primary amine benzylamine is formed to 6 % of total substrate metabolized.
Type:
metabolism
Results:
The N-oxidation of the parent amine was inhibited by CO, SKF525-A, and inhibitors known to interact with microsomal cytochrom P-450. Phenobarbitone pre-treatment stimulates further metabolism of the hydroxylamine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data, in vitro investigation
Details on distribution in tissues:
no data, in vitro investigation
Details on excretion:
no data, in vitro investigation

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
main metabolite: N,N-dibenzylhydroxylamine, identity established by thin-layer-chromatography, , gas-liquid chromatography and combined gas-liquid chromatography
minor metabolite: benzylamine

Applicant's summary and conclusion

Executive summary:

N,N-Dibenzylamine metabolism was studied in vitro by incubation of N,N-dibenzylamine with male rabbit liver 9000g supernatant for 30 minutes. The study has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized , 90 % is converted to N,N-dibenzylhydroxylamine. The primary amine benzylamine is formed to 6 % of total substrate metabolized. The N-oxidation of the parent amine was inhibited by CO, SKF525-A, and inhibitors known to interact with microsomal cytochrom P-450. Phenobarbitone pre-treatment stimulates further metabolism of the hydroxylamine (Beckett 1975).