Indometacin

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

publication

Title:

Cutaneous absorption of indomethacin from two topical preparations in volunteers

Author:

Nowack, H et al.

Year:

1985

Bibliographic source:

Pharmaceutical Research, 2(5): 202-206

Materials and methods

Principles of method if other than guideline:

Seven healthy male human volunteers were treated with indomethacin in different formulations in a cross over design

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

0.5% indomethacin solution (Elmetacin(R)) from Luitpold-Werk, Munique, Germany
1.0% indomethacin solutin (Elmetacin(R)) from Luitpold-Werk, Munique, Germany
1.0% indomethacin gel (Amuno(R)-gel) from by MSD-Frosst-Pharma
50 mg indomethacin tablet (Amuno(R)) from MSD Pharma

Test animals

Species:

human

Sex:

male

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

for 8 hours covered by a plastic foil, thereafter skin was cleaned with cellulose, 24 hours after drug administration skin was cleaned with bland soap

Doses:

oral: 50 mg/subject (140 µmol)
dermal: 50 - 100 mg (140 - 280 µmol) on a skin area of 30 x 40 cm

Results and discussion

Any other information on results incl. tables

Parameter	Tablett (50 mg)	0.5% indomethacin solution	1% indomethacin solution	1% indomethacin gel
Time point of maximum concentration [hours]	2	4-8	4-8	4-8
Maximum concentration [ng/mL]	~ 849	95.2	127.2 (~130)	Compares with 1% solution
Area under Curve (AUC) [ng x h/mL)	5756.5 ± 1336.4	1312.6 ± 712.9	2009.1 ± 389.6	2603.9 ± 1501.0
Relative bioavailability after dermal application [%]		20
Urinary excretion within 48 hours (free and conjugated moieties of indomethacin, O-desmethyl-indomethacin and N-deschloro-benzoyl-indomethacin^a) [µmol]	48.0 ± 11.0	8.5 ± 3.2	11.6 ± 3.3	13.9 ± 6.8
In % of dose:	34.3	6.1	4.1	5.0

Authors resumée:

1% indomethacin gel was comparable with the 1% indomethacin solution (no statistical signíficant difference).

Urinary recovery following oral administration is in the comparable range with other publications considering the different experimental conditions.

Metabolisation is independent from the route of administration