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dc.contributor.authorMcDonnell, C G
dc.contributor.authorMalkan, D
dc.contributor.authorVan Pelt, F D
dc.contributor.authorShorten, G D
dc.date.accessioned2012-02-03T15:09:09Z
dc.date.available2012-02-03T15:09:09Z
dc.date.issued2012-02-03T15:09:09Z
dc.identifier.citationEur J Anaesthesiol. 2003 Aug;20(8):662-7.en_GB
dc.identifier.issn0265-0215 (Print)en_GB
dc.identifier.issn0265-0215 (Linking)en_GB
dc.identifier.pmid12932070en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208983
dc.description.abstractBACKGROUND AND OBJECTIVE: Statins are prescribed for patients with hypercholesterolemia. Atorvastatin is metabolized by cytochrome P4503A4 and inhibits P4503A4 activity in vitro. Alfentanil is a potent opioid used in clinical anaesthetic practice and is also metabolized by P4503A4. This study tested the hypothesis that chronic atorvastatin administration inhibits the metabolism of alfentanil. METHODS: Sixteen patients undergoing elective surgery were studied as matched pairs. One member of each pair was maintained on standard doses of atorvastatin for at least 4 months. Each patient received an alfentanil bolus (80 microg kg(-1)) intravenously (i.v.), followed by an alfentanil infusion (0.67 microg kg(-1) min(-1)) for 90 min. Serial plasma alfentanil concentrations were measured using gas chromatography-nitrogen phosphorous detection. Pharmacokinetic parameters were calculated using two-compartment linear modelling. RESULTS: One patient and the corresponding match were excluded from the analysis. The elimination half-life of alfentanil was similar in the control and atorvastatin groups (98.8 +/- 12.4 versus 98.3 +/- 11.3 min, respectively). The clearance (Cl), volume of distribution at steady-state (Vdss) and area under the curve (AUC) were similar in the two groups (Cl = 0.20 (+/- 0.06) and 0.22 (+/- 0.04) L min(-1), Vdss = 0.38 (+/- 0.07) and 0.39 (+/- 0.07) L kg(-1), AUC = 0.05 (+/- 0.02) and 0.04 (+/- 0.01) mg min mL(-1)). CONCLUSIONS: Concurrent atorvastatin administration does not alter the pharmacokinetics of alfentanil in patients undergoing elective surgery.
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAlfentanil/blood/*pharmacokineticsen_GB
dc.subject.meshAnalgesics, Opioid/blood/*pharmacokineticsen_GB
dc.subject.meshAnticholesteremic Agents/administration & dosage/*pharmacologyen_GB
dc.subject.meshArea Under Curveen_GB
dc.subject.meshChromatography, Gasen_GB
dc.subject.meshDrug Interactions/physiologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHeptanoic Acids/administration & dosage/*pharmacologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHypercholesterolemia/drug therapyen_GB
dc.subject.meshInfusions, Intravenousen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPyrroles/administration & dosage/*pharmacologyen_GB
dc.subject.meshTime Factorsen_GB
dc.titleElimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin.en_GB
dc.contributor.departmentCork University Hospital, Department of Anaesthesia and Intensive Care Medicine, , Wilton, Cork, Ireland. conormcdonnell@hotmail.comen_GB
dc.identifier.journalEuropean journal of anaesthesiologyen_GB
dc.description.provinceMunster
html.description.abstractBACKGROUND AND OBJECTIVE: Statins are prescribed for patients with hypercholesterolemia. Atorvastatin is metabolized by cytochrome P4503A4 and inhibits P4503A4 activity in vitro. Alfentanil is a potent opioid used in clinical anaesthetic practice and is also metabolized by P4503A4. This study tested the hypothesis that chronic atorvastatin administration inhibits the metabolism of alfentanil. METHODS: Sixteen patients undergoing elective surgery were studied as matched pairs. One member of each pair was maintained on standard doses of atorvastatin for at least 4 months. Each patient received an alfentanil bolus (80 microg kg(-1)) intravenously (i.v.), followed by an alfentanil infusion (0.67 microg kg(-1) min(-1)) for 90 min. Serial plasma alfentanil concentrations were measured using gas chromatography-nitrogen phosphorous detection. Pharmacokinetic parameters were calculated using two-compartment linear modelling. RESULTS: One patient and the corresponding match were excluded from the analysis. The elimination half-life of alfentanil was similar in the control and atorvastatin groups (98.8 +/- 12.4 versus 98.3 +/- 11.3 min, respectively). The clearance (Cl), volume of distribution at steady-state (Vdss) and area under the curve (AUC) were similar in the two groups (Cl = 0.20 (+/- 0.06) and 0.22 (+/- 0.04) L min(-1), Vdss = 0.38 (+/- 0.07) and 0.39 (+/- 0.07) L kg(-1), AUC = 0.05 (+/- 0.02) and 0.04 (+/- 0.01) mg min mL(-1)). CONCLUSIONS: Concurrent atorvastatin administration does not alter the pharmacokinetics of alfentanil in patients undergoing elective surgery.


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