title: Metabolism of FK 506 in differentially induced rat liver microsomes.
abstract: The in vitro hepatic metabolism of FK 506 was studied in microsomes prepared from control rats as well as in microsomes prepared from rats treated with the selective cytochrome P-450 isozyme inducers 3-methylcholanthrene (IA), phenobarbital (IIB), and dexamethasone (IIIA). The metabolism of FK 506 was similar for control microsomes and for microsomes prepared from phenobarbital and 3-methylcholanthrene induced animals. The percentage of FK 506 metabolized by these tissue preparations ranged from 21.7 to 32.7%. In contrast, the percentage of FK 506 metabolized by dexamethasone induced microsomes was 86.4%. The metabolism of FK 506 was not effected when the selective IA and IIB isozyme inhibitors alpha-naphthoflavone and orphenadrine were added to the incubations. However, the metabolism of FK 506 decreased by approximately 44% when the IIIA specific isozyme inhibitor troleandomycin was added to the dexamethasone induced microsomes. Therefore, the metabolism of FK 506 is apparently mediated primarily by the steroid inducible cytochrome P-450 IIIA isozyme.
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003907:Dexamethasone; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010634:Phenobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000378:metabolism*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008748:Methylcholanthrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D016559:Tacrolimus; D010634:Phenobarbital