| The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam. | |
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MedLine Citation:
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PMID: 12911366 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Anaesthesia Volume: 58 ISSN: 0003-2409 ISO Abbreviation: Anaesthesia Publication Date: 2003 Sep |
Date Detail:
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Created Date: 2003-08-12 Completed Date: 2003-11-12 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0370524 Medline TA: Anaesthesia Country: England |
Other Details:
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Languages: eng Pagination: 899-904 Citation Subset: AIM; IM |
Affiliation:
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Department of Anaesthesia, Cork University Hospital, Ireland. conormcdonnell@hotmail.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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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