Document Detail


The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.
MedLine Citation:
PMID:  12911366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C G Mc Donnell; S Harte; J O'Driscoll; C O'Loughlin; F N A M Van Pelt; G D Shorten; F D Van Pelt
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anaesthesia     Volume:  58     ISSN:  0003-2409     ISO Abbreviation:  Anaesthesia     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-08-12     Completed Date:  2003-11-12     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0370524     Medline TA:  Anaesthesia     Country:  England    
Other Details:
Languages:  eng     Pagination:  899-904     Citation Subset:  AIM; IM    
Affiliation:
Department of Anaesthesia, Cork University Hospital, Ireland. conormcdonnell@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
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*
Chemical
Reg. No./Substance:
0/Anesthetics, Intravenous; 0/Anticholesteremic Agents; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 110862-48-1/atorvastatin; 59467-70-8/Midazolam
Comments/Corrections
Erratum In:
Anaesthesia. 2003 Nov;58(11):1158
Note: Van Pelt F D [corrected to Van Pelt F N A M]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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