Time-course of hepatic cytochrome p450 subfamily induction by chronic carbamazepine treatment in rats.
Recent studies indicate that carbamazepine (CBZ) induces hepatic cytochrome p450 (CYP) protein subfamilies. The present study examines the time-course of the appearance of hepatic CYP subfamilies (2B, 3A) and serum levels of CBZ and its metabolite, CBZ epoxide (CBZE), induced by CBZ treatment in rats. Male Wistar rats were given 5 g of CBZ (CBZ-treated) per 1 kg of feed for 3, 7, 14, 28 and 42 d or feed without CBZ (control). Serum levels of CBZ and CBZE were evaluated by HPLC. Induction ratios of CYP2B and CYP3A were evaluated by Western blotting. Serum levels of CBZ and CBZE became maximal after 14 and 7 d, respectively, after CBZ treatment. Both levels gradually, then significantly decreased after 42 d CBZ compared with maximal levels. The induction ratio of CYP2B did not differ between 3, 7, 14, 28 and 42 d CBZ treatment. The induction ratio of CYP3A reached a maximum after 14 d CBZ, then significantly decreased after 28 and 42 d CBZ compared to the maximal rate. The difference between CYP2B and CYP3A induction by CBZ chronic treatment is a novel finding.
Yamashita
Hakuei
H
Department of Neuropsychiatry, Saitama Medical School, Moroyama, Saitama, Japan. hymasit@saitama-med.ac.jp
Kazawa
Tetsushi
T
Minatogawa
Yukiko
Y
Ebisawa
Takashi
T
Yamauchi
Toshio
T
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D007527:Isoenzymes; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating