2-phenyl-1H-benzimidazole-5-sulphonic acid

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was approved by an independent ethical committee (Institutional Review Board) operating in accordance with the guidelines of the FDA. All phases of the clinical trial have been audited by the quality assurance unit.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Principles of method if other than guideline:

The skin penetrating potential of phenylbenzimidazole sulfonic acid was investigated in humans using 14C-radiolabelled test item. Six healthy male volunteers (age: 51 – 63 years) were used for this single dose dermal application study. One gram of a gel containing 80 mg of the radiolabelled test item (1.86 MBq) was applied on 333 cm2 on one upper arm of each participant using a spatula. The skin was protected with a non-occlusive cover, not being in contact with the gel. After 6 hours the remaining gel on the skin was removed by skin washings with cotton wool plugs soaked with ether. Thereafter, the whole area of treated skin was stripped 10 times with adhesive films (Scotch® 3M). Blood samples were taken up to 120 hours after gel application. Urine and feces were collected up to 5 days after treatment. Plasma samples, urine, feces, methanol extracts of the cotton wool plugs, and adhesive films were analyzed for total radioactivity using Liquid Scintillation Counting (LSC).

GLP compliance:

no

Remarks:

in compliance with Good Clinical Practice (GCP) Guidelines for trials on medicinal products in the EU

Test material

Test material information

Constituent 1

Reference substance name:

2-phenyl-1H-benzimidazole-5-sulphonic acid

EC Number:

248-502-0

EC Name:

2-phenyl-1H-benzimidazole-5-sulphonic acid

Cas Number:

27503-81-7

Molecular formula:

C13H10N2O3S

IUPAC Name:

2-phenyl-1H-benzimidazole-5-sulphonic acid

Radiolabelling:

yes

Test animals

Species:

human

Sex:

male

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: creme

Doses:

80 mg per person

Results and discussion

Total recovery:

- Total recovery:
- Recovery of applied dose acceptable: yes

Percutaneous absorption

Key result

Dose:

80 mg

Parameter:

percentage

Absorption:

ca. 0.2 %

Remarks on result:

other: after five days

Applicant's summary and conclusion

Conclusions:

From the results of this study the author concluded that no noticeable absorption had taken place after the dermal application of Phenylbenzimidazole sulfonic acid. The low amount of radioactivity excreted in urine and feces within 5 days is in good agreement with the data from plasma measurements, which were always lower than two times the background radioactivity value, thus, confirming the fact that nearly no percutaneous absorption occurred.

Executive summary:

Study Design

The skin penetrating potential of phenylbenzimidazole sulfonic acid was investigated in humans using 14C-radiolabelled test item. Six healthy male volunteers (age: 51 – 63 years) were used for this single dose dermal application study. One gram of a gel containing 80 mg of the radiolabelled test item (1.86 MBq) was applied on 333 cm2 on one upper arm of each participant using a spatula. The skin was protected with a non-occlusive cover, not being in contact with the gel. After 6 hours the remaining gel on the skin was removed by skin washings with cotton wool plugs soaked with ether. Thereafter, the whole area of treated skin was stripped 10 times with adhesive films (Scotch® 3M). Blood samples were taken up to 120 hours after gel application. Urine and feces were collected up to 5 days after treatment. Plasma samples, urine, feces, methanol extracts of the cotton wool plugs, and adhesive films were analyzed for total radioactivity using Liquid Scintillation Counting (LSC).

Results

In general, no maximal plasma levels of total radioactivity were reached. The plasma radioactivity values were below 0.01 µg eq/mL and always lower than two times the background value. In most of the volunteers no noticeable plasma levels of radioactivity were observed, indicating no penetration. Therefore, pharmacokinetic parameters could not be calculated. The recoveries are summarized in the following table:

Medium	Recoveries (of dose applied)
Skin washing with cotton plugs	43.409 – 70.587 %
Skin stripping 6 hrs after application	10.472 – 35.637 %
Skin stripping 5 days after appl.	0.023 – 0.370 %
Fecal excretion	0.028 – 0.046 %
Renal excretion	0.068 – 0.217 %
Total excretion	0.107 – 0.259 %

Conclusion

From the results of this study the author concluded that no noticeable absorption had taken place after the dermal application of Phenylbenzimidazole sulfonic acid. The low amount of radioactivity excreted in urine and feces within 5 days is in good agreement with the data from plasma measurements, which were always lower than two times the background radioactivity value, thus, confirming the fact that nearly no percutaneous absorption occurred.