Dapsone

Dermal absorption

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:

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Principles of method if other than guideline:

Animals were treated topically with formulations (1 mL/kg or 50 mg dapsone) once daily for 28 consecutive days. Levels of dapsone and N-acetyl dapsone concentration was analyzed in non-clinical samples.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dapsone

EC Number:

201-248-4

EC Name:

Dapsone

Cas Number:

80-08-0

Molecular formula:

C12H12N2O2S

IUPAC Name:

4,4'-sulfonyldianiline

Details on test material:

dapsone

Test animals

Species:

rabbit

Strain:

other: No strain information on rabbit is provided. Study also included human information from clinical trials.

Details on test animals or test system and environmental conditions:

Animals wore Elizabethan collars during a four-hour exposure period to prevent ingestion.

Administration / exposure

Duration of exposure:

Rats and rabbits: 28 days
Humans: 14 days

Doses:

50 mg/kg/day for rats and rabbits (28 days), 1.67 mg/kg (single application) for humans

Results and discussion

Total recovery:

Mean AUC values in rats were 32,587 ng h/ml in males and 159,928 ng h/ml in female rats.
Mean AUC in human were 349 ng h/ml and 481 ng h/ml in male and female patients, respectively.
Approximately 10 % of the applied Dapsone were absorbed dermally in male rats and 25 % in female rats. In humans, less than 1 % of the dermally applied dose were absorbed.

Any other information on results incl. tables

Species (Route)	No. of Doses*	Dose (mg/kg/d)	Cmax of males (ng/mL)	Cmax of Females (ng/mL)	AUC of males (ng.hr/mL)	AUC of females (ng.hr/mL)
rat (topical)	28	50	2613	10909	32587	159928
rabbit (topical)	28	50	1469	1864	14916	13427
human (topical)	28	1.37	17.1	22.3	349	481
human (oral)	1	1.67	1375	NA	52641	NA

 

*rat and rabbit data obtained from studies involving daily dosing for 28 days. Clinical topical data obtained from a study where patients were dosed twice daily for 14 days, formulation applied to approx 20% of the body. The human oral data are from a study in which subjects ingested a single 100 mg tablet of dapsone.

Applicant's summary and conclusion

Conclusions:

Following topical dermal application of the formulations, approximately 10% of the applied dapsone was systemically absorbed by male rats, and approximately 25% by female rats.
In rabbits, approximately 16% of the applied dapsone was systemically absorbed by both genders. In humans, less than 1% of a topically applied dose of dapsone is systemically absorbed.

Executive summary:

In the FDA review of non-disclosed studies on the safety pharmacology of a dapsone 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.

Species (Route)	No. of Doses*	Dose (mg/kg/d)	Cmax of males (ng/mL)	Cmax of Females (ng/mL)	AUC of males (ng.hr/mL)	AUC of females (ng.hr/mL)
rat (topical)	28	50	2613	10909	32587	159928
rabbit (topical)	28	50	1469	1864	14916	13427
human (topical)	28	1.37	17.1	22.3	349	481
human (oral)	1	1.67	1375	NA	52641	NA

 

*rat and rabbit data obtained from studies involving daily dosing for 28 days. Clinical topical data obtained from a study where patients were dosed twice daily for 14 days, formulation applied to approx 20% of the body. The human oral data are from a study in which subjects ingested a single 100 mg tablet of dapsone.