Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was performed in a single male to determine dermal absorption.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
dapsone

Administration / exposure

Duration of exposure:
Rats and rabbits: 28 days
Humans: 1 day
Doses:
50 mg/kg/day for rats and rabbits (28 days), 1.67 mg/kg (single application) for humans
Details on study design:
Dapsone and N-acetyl dapsone concentrations in nonclinical samples were analyzed with HPLC and mass spectroscopy. The method was adequately validated and had acceptable limit of quantitation.

Results and discussion

Conversion factor human vs. animal skin:
Rat and rabbit skin absorption is about 20x higher than human skin

Applicant's summary and conclusion

Conclusions:
In the FDA review of non-disclosed studies on the safety pharmacology of a dapson gel it is summarised that topically applied dapsone is bioavailable at 10-20% in rats and rabbits. In humans, less than 1% of a topically applied dose is bioavailable.
Executive summary:

In the FDA review of non-disclosed studies on the safety pharmacology of a dapson gel it is summarised that topically applied dapsone is bioavailable at 10-20% in rats and rabbits. In humans, less than 1% of a topically applied dose is bioavailable.

Rat male (topical)       Dose: 50 mg/kg       Cmax: 2613 ng/ml       AUC: 32587 ng hr/mL

Rat female (topical)      Dose: 50 mg/kg       Cmax: 10909 ng/ml       AUC: 159928 ng hr/mL

Rabbit male (topical)       Dose: 50 mg/kg       Cmax: 1469 ng/ml       AUC: 14916 ng hr/mL

Rabbit female (topical)      Dose: 50 mg/kg       Cmax: 1864 ng/ml       AUC: 13427 ng hr/mL

Human male (topical)       Dose: 1.37 mg/kg       Cmax: 17.1 ng/ml       AUC: 349 ng hr/mL

Human female (topical)      Dose: 1.37 mg/kg       Cmax: 22.3 ng/ml       AUC: 481 ng hr/mL

Human male (oral)       Dose: 1.67 mg/kg       Cmax: 1375 ng/ml       AUC: 52641 ng hr/mL