Enoxacin is an inducer of CYP1A2 in rat liver.
The induction of cytochrome P450 by enoxacin, ciprofloxacin, and ofloxacin was investigated in female Wistar rats. Animals were treated orally with daily doses ranging from 10 to 400 mg enoxacin per kg body wt, 400 mg ciprofloxacin, or 400 mg ofloxacin per kg body wt for up to 7 days. Activities of methoxyresorufin O-demethylase (MROD) and ethoxyresorufin O-deethylase (EROD) were determined fluorimetrically in hepatic microsomes. MROD activity was increased 2.6-fold after treatment with 100 mg enoxacin per kg body wt for 7 days. Lower doses of enoxacin did not induce MROD activity significantly. Antipeptide antibodies directed specifically against different rat cytochrome P450 enzymes demonstrated that CYP1A2, but not CYP1A1, was induced in rats treated with enoxacin. After ciprofloxacin or ofloxacin treatment, no induction of MROD or EROD activity was observed. Neither ciprofloxacin nor ofloxacin caused any change in CYP1A1 or CYP1A2 apoprotein levels. Further investigations with antipeptide antibodies showed that there was no induction of CYP2B1, CYP2B2, CYP2E1, CYP3A1, CYP3A2, CYP4A1, or CYP4A2 following treatment with enoxacin, ciprofloxacin, or ofloxacin. It is concluded that enoxacin, but not ciprofloxacin or ofloxacin, is an inducer of CYP1A2 in rat liver.
Schulz
T G
TG
Institute of Toxicology and Embryopharmacology, Freie Universität Berlin, Germany.
Stahlmann
R
R
Edwards
R J
RJ
Debri
K
K
Davies
D S
DS
Neubert
D
D
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000906:Antibodies; D000918:Antibody Specificity; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015365:Enoxacin / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D000906:Antibodies; D007527:Isoenzymes; D015365:Enoxacin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A