Reactome | CYP3A4 monooxygenates ATVL to 2-OH-ATVL

CYP3A4 monooxygenates ATVL to 2-OH-ATVL

Stable Identifier

R-HSA-9756138

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, cytosol

ReviewStatus

5/5

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Atorvastatin lactone (ATVL) is hydroxylated to hydroxy-metabolites, predominantly by cytochrome P450 3A4 (CYP3A4) (Park et al. 2008). Statin lactones are metabolized to a much higher extent than their acid forms by CYP enzymes, suggesting that metabolism of the lactone is the relevant pathway for atorvastatin elimination (Jacobsen et al. 2000, Fujino et al. 2004, Filppula et al. 2021). Described here is the formation of 2-hydroxyatorvastatin lactone (2-OH-ATVL).

Literature References

PubMed ID	Title	Journal	Year
34045219	Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins Viinamäki, J, Parviainen, H, Hirvensalo, P, Niemi, M, Ivaska, VE, Filppula, AM, Kurkela, M, Deng, F, Neuvonen, M, Lönnberg, KI	Drug Metab Dispos	2021
18720283	Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin Park, JE, Kim, KB, Moon, BS, Shin, JG, Bae, SK, Liu, KH	Xenobiotica	2008
15801541	Metabolic properties of the acid and lactone forms of HMG-CoA reductase inhibitors Fujino, H, Sakaeda, T, Saito, T, Tsunenari, Y, Kojima, J	Xenobiotica	2004
11038166	Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin Sewing, KF, Soldner, A, Christians, U, Jacobsen, W, Kirchner, G, Benet, LZ, Kuhn, B, Kollman, PA	Drug Metab Dispos	2000