Percutaneous absorption of Octopirox

• Published in: Food and chemical toxicology Vol. 26; no. 1; pp. 53 - 58
• Main Authors: Black, J.G., Kamat, V.B.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1988; New York, NY Elsevier Science
• Subjects: Administration, Oral; Administration, Topical; Animals; Biological and medical sciences; Dermatologic Agents - administration & dosage; Dermatologic Agents - metabolism; Domestic and cosmetic products toxicology; Drug Combinations - administration & dosage; Drug Combinations - metabolism; Ethanolamines - administration & dosage; Ethanolamines - metabolism; Female; Male; Medical sciences; Pyridones - administration & dosage; Pyridones - metabolism; Rats; Skin - metabolism; Toxicology; Vertebrata; Mammalia; Absorption; Rat; Animal; Rodentia; Metabolism; Antidandruff shampoo; Percutaneous route
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/0278-6915(88)90041-5

[ 14C]Octopirox administered to rats by intubation or injection was excreted mostly in the faeces (65–85% of the dose) with smaller amounts (6–19%) in the urine. Blood levels after intubation of Octopirox (4.8 mg/kg body weight) reached a maximum equivalent to 0.137 μg/ml at 2 hr and declined to 0.007 μg/ml at 48 hr after administration. Tissue levels were low, the greatest was the liver with the equivalent of 3 μg Octopirox at 6 hr after intubation. With female rats skin penetration of Octopirox at 1% (v/v) in shampoo without rinsing was 65.1 μg/cm 2 under non-occlusive conditions for 48 hr. When the skin was rinsed after a 10-min contact, penetration was reduced to 3.4 μg/cm 2 under occlusive, and 2.0 μg/cm 2 under non-occlusive conditions. Skin penetration of Octopirox was dependent on duration of contact up to 10 min before rinsing. Penetration at 1% Octopirox increased significantly from 2.4 μg/cm 2 after 2.5 min exposure to 4.5 μg/cm 2 after 10 min contact, but there is no increase in penetration with a 20-min application. Skin penetration Octopirox concentration between 0.1 and 1% (w/v); skin penetration increased from 0.31 to 3.6 μg/cm 2 while deposition increased from 0.8 to 7.6 μg/cm 2. There was no significant difference between the penetration through clipped skin and hairy skin from an application of 1% Octopirox for 5 min followed by rinsing. Under non-occlusive conditions, penetration was 1.5 μg/cm 2 for both types of skin. Blood levels after topical application (15.4 mg/kg body weight) without rinsing and with occlusion reached the equivalent of 0.32 μg/ml at 6 hr. However, when the skin was rinsed and protected with a non-occlusive patch blood levels were reduced to a maximum equivalent to 0.02 μg/ml at 1 hr after application. The safety factor estimated for the consumer using a shampoo containing 1% Octopirox is 29,400, so that the possibility of systemic effects due to absorption through the skin is remote.