1-(dimethylamino)propan-2-ol

Basic toxicokinetics

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

Test material information

Constituent 1

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.