Influence of oral isotretinoin on hepatic and cutaneous P-450-dependent isozyme activities.
Oral administration of isotretinoin (13-cis-retinoic acid) (6 mg/kg per day), 0.05% hexachlorobenzene (HCB) or both drugs simultaneously for 10 days to female Wistar rats caused a statistically significant induction of aminopyrine-N-demethylase (ADM), 7-ethoxyresorufin-O-deethylase (7-ERO-D) and erythromycin-N-demethylase (EMDM) in the liver microsomes. Oral administration of isotretinoin alone or together with HCB induced a marked induction of 7-ERO-D and EMDM in the skin. Administration of isotretinoin alone for 60 days resulted in the induction of EMDM in the liver microsomes, and in combination with HCB caused a statistically significant induction of all hepatic isozymes. HCB alone caused a marked induction of only 7-ERO-D in the skin. These results clearly show that oral isotretinoin is capable of inducing hepatic and cutaneous microsomal P-450-dependent catalytic activities. It remains to be elucidated whether the induction of these enzymes is of importance for the therapeutic action of isotretinoin.
Goerz
G
G
Department of Dermatology, Heinrich-Heine University, Düsseldorf, Germany.
Bolsen
K
K
Kalofoutis
A
A
Tsambaos
D
D
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006581:Hexachlorobenzene / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D015474:Isotretinoin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000201:enzymology*
D007527:Isoenzymes; D006581:Hexachlorobenzene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D015474:Isotretinoin