Rifabutin autoinduction is caused by involvement of cytochrome P450 and cholinesterase.
Rifabutin exhibits remarkable autoinduction of its elimination, but the mechanism behind it was not fully known. Our work showed that rifabutin administration increased the metabolism of rifabutin itself in both in vivo studies and liver perfusion, and the half-life was decreased by 71.08% and 12.74%, respectively. Further results showed that rifabutin administration increased CYP3A, CYP2D and cholinesterase levels by 87.2%, 57.3% and 65.14%, respectively. The autoinduction phenomenon of rifabutin may, therefore, be attributed to induction of cholinesterase and CYP450 isoenzymes, such as
Zhaoxu
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L
School of Chemical Biology and Pharmaceutical Science, Capital Medical University, Beijing, China.
Jingcheng
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T
Jinnan
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Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002802:Cholinesterases / Q000096:biosynthesis* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D017828:Rifabutin / Q000493:pharmacokinetics* / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D017828:Rifabutin; D003577:Cytochrome P-450 Enzyme System; D002802:Cholinesterases