The negligible systemic availability of retinoids with multiple and excessive topical application of isotretinoin 0.05% gel (Isotrex) in patients with acne vulgaris.
The potential systemic availability of retinoids from topically applied isotretinoin was assessed in 12 men with acne vulgaris. Isotretinoin 0.05% gel was applied to patients at a daily dose of 20 gm (equivalent to 10 mg of isotretinoin) over a 1900 cm2 surface area of skin on the face, back, and chest for 30 days. Blood samples were collected throughout the study and up to 48 hours after the last topical application; they were assayed for isotretinoin, tretinoin, and 4-oxo-isotretinoin by specific high-performance liquid chromatography. Plasma concentrations of isotretinoin, tretinoin, and 4-oxo-isotretinoin were not measurable (less than 20 ng/ml) at any time. Most adverse experiences were cutaneous; a few systemic adverse experiences were judged to be remotely related to topical drug administration. The lack of measurable plasma concentrations of isotretinoin, tretinoin, or 4-oxo-isotretinoin and systemic adverse experiences indicates negligible systemic availability of retinoids even after multiple application of isotretinoin 0.05% gel at doses approximately 12 times greater than normal daily use.
Jensen
B K
BK
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
McGann
L A
LA
Kachevsky
V
V
Franz
T J
TJ
D000152:Acne Vulgaris / Q000188:drug therapy*; D000279:Administration, Cutaneous; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D008297:Male; D014212:Tretinoin / Q000031:analogs & derivatives / Q000097:blood
D005782:Gels; C002202:4-oxoretinoic acid; D014212:Tretinoin; D015474:Isotretinoin