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    The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.

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    Authors
    Mc Donnell, C G
    Harte, S
    O'Driscoll, J
    O'Loughlin, C
    Van Pelt, F N A M
    Shorten, G D
    Affiliation
    Department of Anaesthesia, Cork University Hospital, Ireland., conormcdonnell@hotmail.com
    Issue Date
    2012-02-03T15:09:19Z
    MeSH
    Aged
    Anesthesia, General
    Anesthetics, Intravenous/*blood
    Anticholesteremic Agents/*pharmacology
    Drug Interactions
    Female
    Half-Life
    Heptanoic Acids/*pharmacology
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
    Male
    Matched-Pair Analysis
    Midazolam/*blood
    Middle Aged
    Pyrroles/*pharmacology
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    Citation
    Anaesthesia. 2003 Sep;58(9):899-904.
    Journal
    Anaesthesia
    URI
    http://hdl.handle.net/10147/208990
    PubMed ID
    12911366
    Abstract
    Midazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. Atorvastatin is also metabolised by cytochrome P450 3A4 and, in vitro, atorvastatin inhibits the cytochrome P450 3A4-mediated metabolism of mexazolam. We hypothesised that concurrent administration of atorvastatin and midazolam would result in altered midazolam pharmacokinetics. Fourteen patients scheduled to undergo general anaesthesia for elective surgery were recruited in a matched pair design to receive intravenous midazolam (0.15 mg.kg-1). Of these patients, seven were taking long-term atorvastatin. Atorvastatin patients demonstrated a greater area under the curve (889.4 (standard deviation 388.6) ng-h.ml-1) vs. control patients (629.1 (standard deviation 197.2) ng-h.ml-1) (p < 0.05). Patients taking atorvastatin also demonstrated a decreased clearance (0.18 (standard deviation 0.08) l-kg. h-1) vs. control patients (0.27 (standard deviation 0.08) l-kg.h-1) (p < 0.05). This study suggests that chronically administered atorvastatin decreases the clearance of intravenously administered midazolam.
    Language
    eng
    ISSN
    0003-2409 (Print)
    0003-2409 (Linking)
    Collections
    Cork University Hospital

    entitlement

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