Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication, which meets basic scientific principles.

Data source

Reference
Title:
No information
Author:
Streeter D.G. und Pfadenhauer E.H.: Drug Metabolism and|Disposition, 12, 199-203, (1984)

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Urinary excretion products derived from [14C]-radiolabelled N,N-dimethylaminoisopropanol were determined following single i.v. and oral administration to rhesus monkeys
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(dimethylamino)propan-2-ol
EC Number:
203-556-4
EC Name:
1-(dimethylamino)propan-2-ol
Cas Number:
108-16-7
Molecular formula:
C5H13NO
IUPAC Name:
1-(dimethylamino)propan-2-ol
Test material form:
liquid
Specific details on test material used for the study:
- namr of test material as cited in the publication: Dimethylaminoisopropanol

SOURCE OF TEST MATERIAL, unlabelled test substance
- Source and lot/batch number of test material: Newport, PharmaceuticalsLot No. 4795-GK- 105.

RADIOLABELLING INFORMATION (if applicable)
- Source: radiolabelled test substance was synthesized by California Bionuclear Corp., Sun VaIley, CA.
- Radiochemical purity: 98%.
- Specific activity: 7.6 mCi/mmol.
- Locations of the label: [3-14C]-labeled NN-dimethylamino-2-propanol.


Radiolabelling:
yes
Remarks:
C14

Test animals

Species:
monkey
Strain:
other:
Remarks:
Rhesus

Administration / exposure

Route of administration:
other: oral and i.v.
Details on exposure:
Six animals were administered by nasogstric intubation, six animals received i.v. doses through an indwelling catheter in the saphenous vein.
Duration and frequency of treatment / exposure:
single administration
No. of animals per sex per dose / concentration:
6 per administration route
Details on dosing and sampling:
- Urine samples were collected continously by an indwelling urinary catheter for 8 hours after administration.In the 12- through 72-hr period, urine samples were collected by means of an urine collection funnel which emptied into collection botles.
- The primary analytical system or metabolite quantification was TLC and autoradiographic analysis.

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
A single metabolite derived from [14C]-radiolabelled N,N-dimethylaminoisopropanol was identified as N,N-dimethylaminoisopropanol-N-oxide.
This Metabolite accounted for 17 - 18% of the administrated radioactivity in either the i.v. or orally dosed animals.
48% (i.v.) nd 55% (oral) of the total radioactivity were assigned to the parent compound.
The proportions of dimethylaminoisopropanol-N-oxide and dimethylaminoisopropanol appeared to be unaffected by route of administration, with the parent compound dominating in both cases.

Applicant's summary and conclusion

Conclusions:
Dimethylaminoisopropanol is mostly excreted as the original substance after i.v. and oral administration to the rhesus monkey. The only observed metabolite is dimethylaminoisopropanol-N-oxide.