Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro

Conor G. Mc Donnell; G. Shorten; F. N.A.M. Van Pelt

doi:10.1111/j.1365-2044.2005.04110.x

Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro

Conor G. Mc Donnell
, G. Shorten
, F. N.A.M. Van Pelt

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (Km) of 5.25 (SD 1.2) μmol.1-1. Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (Ki) of 12.4 (95% CI 4.65-20.06) μmol.1-1. Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a Ki of 94.3 (95% CI 55.01-133.5) μmol.1-1. Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro. © 2005 Blackwell Publishing Ltd.

Original language	English (Ireland)
Pages (from-to)	747-753
Number of pages	7
Journal	Anaesthesia
Volume	60
Issue number	8
DOIs	https://doi.org/10.1111/j.1365-2044.2005.04110.x
Publication status	Published - Aug 2005

Access to Document

10.1111/j.1365-2044.2005.04110.x

Cite this

@article{cd4b62b7fa7a4d5b943acffd965c5d6e,

title = "Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro",

abstract = "We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (Km) of 5.25 (SD 1.2) μmol.1-1. Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (Ki) of 12.4 (95\% CI 4.65-20.06) μmol.1-1. Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a Ki of 94.3 (95\% CI 55.01-133.5) μmol.1-1. Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro. {\textcopyright} 2005 Blackwell Publishing Ltd.",

author = "\{Mc Donnell\}, \{Conor G.\} and G. Shorten and \{Van Pelt\}, \{F. N.A.M.\}",

year = "2005",

month = aug,

doi = "10.1111/j.1365-2044.2005.04110.x",

language = "English (Ireland)",

volume = "60",

pages = "747--753",

journal = "Anaesthesia",

issn = "0003-2409",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "8",

}

TY - JOUR

T1 - Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro

AU - Mc Donnell, Conor G.

AU - Shorten, G.

AU - Van Pelt, F. N.A.M.

PY - 2005/8

Y1 - 2005/8

N2 - We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (Km) of 5.25 (SD 1.2) μmol.1-1. Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (Ki) of 12.4 (95% CI 4.65-20.06) μmol.1-1. Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a Ki of 94.3 (95% CI 55.01-133.5) μmol.1-1. Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro. © 2005 Blackwell Publishing Ltd.

AB - We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (Km) of 5.25 (SD 1.2) μmol.1-1. Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (Ki) of 12.4 (95% CI 4.65-20.06) μmol.1-1. Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a Ki of 94.3 (95% CI 55.01-133.5) μmol.1-1. Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro. © 2005 Blackwell Publishing Ltd.

UR - https://www.mendeley.com/catalogue/7f91d5d5-1440-37eb-a4b7-73f1aa697dc9/

U2 - 10.1111/j.1365-2044.2005.04110.x

DO - 10.1111/j.1365-2044.2005.04110.x

M3 - Article

C2 - 16029222

SN - 0003-2409

VL - 60

SP - 747

EP - 753

JO - Anaesthesia

JF - Anaesthesia

IS - 8

ER -

Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro

Abstract

Access to Document

Other files and links

Fingerprint

Cite this