Fusidic acid

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Principles of method if other than guideline:

Study with eight male rabbits (New Zealand White). An area 6 cm x 10cm was shaved on the back of the rabbits. Four of the rabbits were treated with 1% sodium lauryl sulphate in vaseline. The remaining four rabbits were untreated. After 24 hours ca. 1g of salve was applied to the shaved area of all eight rabbits. Blood samples were taken after 0,2,4,6,8,24 and 48 hours after application.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Fusidic acid

EC Number:

230-256-0

EC Name:

Fusidic acid

Cas Number:

6990-06-3

Molecular formula:

C31H48O6

IUPAC Name:

2-[(1Z,2S,3aS,3bS,5aS,6S,7R,9aS,9bS,10R,11aR)-2-(acetyloxy)-7,10-dihydroxy-3a,3b,6,9a-tetramethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoic acid

Test material form:

solid: crystalline

Details on test material:

Details are given for each individual study

Specific details on test material used for the study:

Salve containing 2% tritiated fucidin in fucidin salve (without lanolin) containing 0.68 mCi/g

Radiolabelling:

yes

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

Body weight between 2.55 and 3.05 kg.

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Duration of exposure:

48 hours

Doses:

1 g salve of 0.68 mCi/g

No. of animals per group:

8

Control animals:

no

Details on study design:

An area 6 cm x 10cm was shaved on the back of the rabbits. Four of the rabbits were treated with 1% sodium lauryl sulphate in vaseline. The remaining four rabbits were untreated. After 24 hours ca. 1g of salve was applied to the shaved area of all 8 rabbits. Blood samples were taken after 0,2,4,6,8,24 and 48 hours after application. The animals were kept in stocks for the first 24 hours after application.

Serum was prepared from the blood samples. The serum samples were counted for up to 50 minines each in a Beckman CPM-100 liquid scintillation counter. Counting efficiency was determined from a previously prepared external standard quench correction curve.

Results and discussion

Absorption in different matrices:

Counts in serum from rabbits pretreated with lauryl sulphate were 3-45 times greater than in blank serum. In the untreated rabbits, many of the counts were less than twice blank.
Mean levels in the pretreated rabbits were roughly 10 times levels in the untreated animals. The highest single concentration obtained in any animal whilst in the stocks was 3.4 % dose/rabbit in pretreated animals, and 0.16% in intact animals.

Any other information on results incl. tables

The % dose absorbed was calculated assuming a distribution volume of 1 L/kg and was in pretreated rabbits 0.2-3.4% dose/rabbit and 0.02-0.16% in intact animals.

Mean % dose/rabbit at various time after dosing

Rabbit	2 hours	4 hours	6 hours	8 hours	24 hours
1 - pretreated	0.547	0.702	3.357	0.790	1.824*
2 - pretreated	2.023	0.911	1.195	1.174	0.737
3 - pretreated	0.300	0.965	0.356	0.322	0.200
4 - pretreated	0.692	0.694	0.630	0.416	0.210
Mean - pretreated	0.891	0.818	1.454	0.676	0.743
5 - unchanged skin	0.033	0.116	0.088	0.101	2.284*
6 - unchanged skin	0.040	0.078	0.076	0.084	0.069
7 - unchanged skin	0.045	0.047	0.114	0.065	0.155
8 - unchanged skin	0.015	Not valid	0.028	0.020	0.073
Mean - unchanged skin	0.033	0.080	0.077	0.068	0.0645

* Removed from stocks after 8 hours

Only blood samples obtained at times when the rabbit is confined in stocks are a valid expression of cutaneous absorption, since samples obtained later (48 hour) were in general higher and this is taken as evidence of oral absorption.

Counts in serum from rabbits pretreated with lauryl sulphate were 3-45 times greater than in blank serum. In the untreated rabbits, many of the counts were less than twice blank.

Mean levels in the pretreated rabbits were roughly 10 times levels in the untreated animals. The highest single concentration obtained in any animal whilst in the stocks was 3.4 % dose/rabbit in pretreated animals, and 0.16% in intact animals.

Applicant's summary and conclusion

Conclusions:

The dermal absorption of sodium fusidate is very low, 0.02-0.16% based on results from a study in rabbits.

Executive summary:

A dermal absorption study Study with eight male rabbits (New Zealand White) was performed. An area 6 cm x 10cm was shaved on the back of the rabbits. Four of the rabbits were treated with 1% sodium lauryl sulphate in vaseline. the remaining four rabbits were untreated. After 24 hours ca. 1g of salve was applied to the shaved area of all 8 rabbits. Blood samples were taken after 0,2,4,6,8,24 and 48 hours after application.

Serum levels in pretreated rabbits were 3-45 times greater than in blank serum. Levels in animals with intact skin were substantially lower.

The % dose absorbed was calculated assuming a distribution volume of 1 L/kg and was in pretreated rabbits 0.2-3.4% dose/rabbit and 0.02-0.16% in intact animals.