Absorption of tretinoin in rats and rabbits following oral and dermal application.
To assess the teratogenic potential of Airol cream (0.05% tretinoin, CAS 302-79-4), plasma concentrations were compared after repeated dermal applications of the maximum dose which could be applied reliably and after oral administration of the highest non-teratogenic dose. The test preparation was applied dermally in two equal portions to rats and rabbits at 2 g/animal/d (equivalent to a tretinoin dose of 3.7 mg/kg/d) and at 6 g/kg/d (equivalent to 3 mg tretinoin/kg/d), respectively. After a single oral administration of 2 mg/kg, Cmax and AUC for tretinoin in rat plasma were 285 +/- 14.6 ng/ml and 595 +/- 123 ng h/ml, respectively. Corresponding values for the rabbit were 78.4 +/- 16.9 ng/ml and 126 +/- 25.4 ng h/ml. In both species, plasma concentrations of tretinoin after dermal application were consistently below the assay quantification limit (< 5 ng/ml and < 2 ng/ml for rat and rabbit, respectively), despite marked irritation of the skin. Thus repeated topical application of the test preparation produced plasma concentration of tretinoin which were well below the plasma concentrations produced by a non-teratogenic oral dose of 2 mg/kg in the rat and rabbit.
Chou
R
R
Pharma Division, Preclinical Research, F. Hoffmann-La Roche AG, Basel, Switzerland.
Bürgin
H
H
Schmitt
G
G
Eggers
H
H
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D007408:Intestinal Absorption; D008297:Male; D011817:Rabbits; D051381:Rats; D012869:Skin Absorption; D013056:Spectrophotometry, Ultraviolet; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D003879:Dermatologic Agents; D014212:Tretinoin