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

  • C. G. McDonnell (a1), D. Malkan (a1), F. D. Van Pelt (a2) and G. D. Shorten (a1)

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.

Copyright

Corresponding author

Correspondence to: Conor McDonnell, Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, Wilton, Cork, Ireland. E-mail: conormcdonnell@hotmail.com Tel: +353 21 4546400 ext. 22134/22135 and +353 86 3572570; Fax: +353 21 4546434

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Keywords

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

  • C. G. McDonnell (a1), D. Malkan (a1), F. D. Van Pelt (a2) and G. D. Shorten (a1)

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