Percutaneous absorption of Octopirox.
[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 micrograms/ml at 2 hr and declined to 0.007 micrograms/ml at 48 hr after administration. Tissue levels were low, the greatest was the liver with the equivalent of 3 micrograms Octopirox at 6 hr after intubation. With female rats skin penetration of Octopirox at 1% (v/v) in shampoo without rinsing was 65.1 micrograms/cm2 under non-occlusive conditions for 48 hr. When the skin was rinsed after a 10-min contact, penetration was reduced to 3.4 micrograms/cm2 under occlusive, and 2.0 micrograms/cm2 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 micrograms/cm2 after 2.5 min exposure to 4.5 micrograms/cm2 after 10 min contact, but there was no further increase in penetration with a 20-min application. Skin penetration and deposition of Octopirox were both proportional to Octopirox concentration between 0.1 and 1% (w/v); skin penetration increased from 0.31 to 3.6 micrograms/cm2 while deposition increased from 0.8 to 7.6 micrograms/cm2. 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 micrograms/cm2 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 micrograms/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 micrograms/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.
Black
J G
JG
Environmental Safety Laboratory, Unilever Research, Sharnbrook, Bedford, England.
Kamat
V B
VB
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000378:metabolism*; D004338:Drug Combinations / Q000008:administration & dosage / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D008297:Male; D011728:Pyridones / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000378:metabolism*
D003879:Dermatologic Agents; D004338:Drug Combinations; D004983:Ethanolamines; D011728:Pyridones; C052599:piroctone olamine