The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.
Mc Donnell, C G Harte, S O'Driscoll, J O'Loughlin, C Van Pelt, F N A M Shorten, G D
Mc Donnell, C G
Harte, S
O'Driscoll, J
O'Loughlin, C
Van Pelt, F N A M
Shorten, G D
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Date
2012-02-03T15:09:19Z
Date Submitted
Keywords
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Subject 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
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
Planned Date
Start Date
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Principal Investigators
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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
Citation
ISSN
0003-2409 (Print)
0003-2409 (Linking)
0003-2409 (Linking)
eISSN
ISBN
DOI
PMID
12911366