Pirfenidone 5-hydroxylation is mainly catalysed by CYP1A2 and partly catalysed by CYP2C19 and CYP2D6 in the human liver.
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Zhang Y, Sato R, Fukami T, Nakano M, Nakajima M
Pirfenidone 5-hydroxylation is mainly catalysed by CYP1A2 and partly catalysed by CYP2C19 and CYP2D6 in the human liver.
Xenobiotica. 2021 Dec;51(12):1352-1359. doi: 10.1080/00498254.2021.2007553. Epub 2021 Nov 30.
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- 34779706 [ View in PubMed]
- Abstract
Pirfenidone is a first-line drug for the treatment of idiopathic pulmonary fibrosis. The primary metabolic pathways of pirfenidone in humans are 5-hydroxylation and subsequent oxidation to 5-carboxylpirfenidone. The aims of this study were to determine the cytochrome P450 isoforms responsible for pirfenidone 5-hydroxylation and to evaluate their contributions in human liver microsomes (HLM).Among the recombinant P450 isoforms, CYP1A2, CYP2D6, CYP2C19, CYP2A6, and CYP2B6 were shown to catalyse the 5-hydroxylation of pirfenidone. Pirfenidone 5-hydroxylase activity by HLM was inhibited by alpha-naphthoflavone (by 45%), 8-methoxypsolaren (by 84%), tranylcypromine (by 53%), and quinidine (by 15%), which are CYP1A2, CYP1A2/CYP2A6/CYP2C19, CYP2A6/CYP2C19, and CYP2D6 inhibitors, respectively.In 17 individual HLM donors, pirfenidone 5-hydroxylase activity was significantly correlated with phenacetin O-deethylase (r = 0.89, P < 0.001) and S-mephenytoin 4'-hydroxylase activities (r = 0.51, P < 0.05), which are CYP1A2 and CYP2C19 marker activities, respectively.By using the relative activity factors, the contributions of CYP1A2, CYP2C19, and CYP2D6 to pirfenidone 5-hydroxylation in the human liver were 72.8%, 11.8%, and 8.9%, respectively.In conclusion, we clearly demonstrated the predominant P450 involved in pirfenidone 5-hydroxylation in the human liver is CYP1A2, with CYP2C19 and CYP2D6 playing a minor role.
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Reaction Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwarePirfenidoneFluvoxamine The metabolism of Pirfenidone can be decreased when combined with Fluvoxamine. PirfenidoneEnoxacin The metabolism of Pirfenidone can be decreased when combined with Enoxacin. PirfenidoneRofecoxib The metabolism of Pirfenidone can be decreased when combined with Rofecoxib. PirfenidoneQuinidine The metabolism of Pirfenidone can be decreased when combined with Quinidine. PirfenidoneTechnetium Tc-99m ciprofloxacin The metabolism of Pirfenidone can be decreased when combined with Technetium Tc-99m ciprofloxacin.
