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Elimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin

Published online by Cambridge University Press:  12 July 2005

C. G. McDonnell ,
D. Malkan ,
F. D. Van Pelt  and
G. D. Shorten
C. G. McDonnell
Affiliation:
Cork University Hospital, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
D. Malkan
Affiliation:
Cork University Hospital, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
F. D. Van Pelt
Affiliation:
University College Cork, Department of Pharmacology and Therapeutics, Cork, Ireland
G. D. Shorten
Affiliation:
Cork University Hospital, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
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Abstract

Summary

Background 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 μg kg−1) intravenously (i.v.), followed by an alfentanil infusion (0.67 μg 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.

Keywords

ANAESTHESIA, INTRAVENOUSANALGESICS, OPIOID, alfentanilCHEMICAL AND PHARMACOLOGICAL PHENOMENA, drug interactionsENZYME INHIBITORS, hydroxymethylglutaryl-CoA reductase inhibitorsMETABOLISM, area under the curve, biotransformation, pharmacokinetics
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 8 , September 2003 , pp. 662 - 667
Copyright
2003 European Society of Anaesthesiology

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