Fluocortolone

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

other: expert statement

Adequacy of study:

other information

Study period:

not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well reported expert statement

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Healthy volunteers and psoriasis patients were exposed to fluocortolone cremes (0.25% w/w fluocortolone) for 1 to 24 hours. Skin was stripped 20 times afterwards to determine amount of resorbed substance.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Fluocortolone

EC Number:

205-811-5

EC Name:

Fluocortolone

Cas Number:

152-97-6

Molecular formula:

C22H29FO4

IUPAC Name:

(1S,2R,3aS,3bS,5S,9aR,9bS,10S,11aS)-5-fluoro-10-hydroxy-1-(2-hydroxyacetyl)-2,9a,11a-trimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one

Details on test material:

- Name of test material (as cited in study report): fluocortolone (ZK 10445)

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: healthy volunteers and psoriasis patients

Sex:

not specified

Administration / exposure

Type of coverage:

other: open and occlusive dressing

Vehicle:

other: mainly water based

Duration of exposure:

1, 2, 4 and 8 hours on healthy volunteers;
25 hours on psoriasis patients

Doses:

0.25% w/w fluocortolone creme was used. Amount applied varied.

No. of animals per group:

11 volunteers,
number of psoriasis patients not reported

Control animals:

no

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Dose:

no data

Parameter:

percentage

Absorption:

ca. 44 %

Remarks on result:

other: 8 hours exposure

Remarks:

healthy volunteers

Percutaneous absorption 2

Parameter:

percentage

Absorption:

ca. 65 %

Remarks on result:

other: 24 hours

Remarks:

psoriasis patients

Conversion factor human vs. animal skin:

no conversion factor needed

Any other information on results incl. tables

The resorption rate increased with increasing exopsure time.

After 8 hours exposure a dermal penetration rate of 44% in mean was found. After 12 and 20 times skin stripping the penetration rate could be increased to 10 and 20 %, respectively. No relevant differences between occlusiv and open application was found.

Psoriasis patients treated 24 hours had dermal resorption rates of 65 % (SD 5%).

Fatty cremes had approximately half of the penetration rates of water based cremes.

Applicant's summary and conclusion

Conclusions:

Dermal penetration rate of fluocortolone in humans (healty volunteers) is ca 44%.

Executive summary:

Dermal absorption of fluocortolone creme as emulsion was tested on eleven healthy volunteers at different time points. It was shown that the resorption rate was increased with increasing exopsure time. After 8 hours exposure a dermal penetration rate of 44% in mean was found. After 12 and 20 times skin stripping the penetration rate could be increased to 10 and 20 %, respectively. Relevant differences between occlusiv and open application of test substance was not seen. When psoriasis patients were treated 24 hours with fluocortolone creme resorption rates of 65 % (5% SD) were found. Testing of water-based and fat-based cremes revealed that fatty cremes have approximately half of the penetration rate compared to water based cremes.