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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)



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.


Corresponding author

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


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Erikssen J, Madsen S. Treatment of hypercholes- terolemia with statins. Tidsskr Nor Laegeforen 1997; 117: 32163220.
Prueksaritanont T, Gorham LM, Ma B, et al. In vitro metabolism of simvastatin in humans [SBT] identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 1997; 25: 11911199.
Chang GWM, Kam PCA. The physiological and pharmacological roles of cytochrome P450 isoenzymes. Anaesthesia 1999; 54: 4250.
Nelson DR, Koymans L, Kamtaki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6: 142.
Segaert MF, De Soete C, Vandwiele I, Verbanck J. Drug interaction-induced rhabdomyolysis. Nephrol Dial Transplant 1996; 11: 18461847.
Guitton J, Buronfosse T, Desage M, et al. Possible involvement of multiple cytochrome P450s in fentanyl and sufentanil metabolism as opposed to alfentanil. Biochem Pharmacol 1997; 53: 16131619.
Labroo RB, Thummel KE, Kunze KL, Podoll T, Trager WF, Kharasch ED. Catalytic role of cytochrome P450 3A4 in multiple pathways of alfentanil metabolism. Drug Metab Dispos 1995; 23: 490496.
Janicki PK, James MFM, Erskine WAR. Propofol inhibits enzymatic degradation of alfentanil and sufentanil by isolated liver microsomes in vitro. Br J Anaesth 1992; 68: 311312.
Meistelman C, Saint-Maurice C, Lepaul M. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987; 66: 1316.
Gibaldi M, Perrier D. Pharmacokinetics, 2nd edn. New York, USA: Marcel Dekker, 1982.
Kharasch ED, Russell M, Mautz D, et al. The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 1997; 87: 3650.
Meuldermans W, Van Peer A, Hendrickx J, et al. Alfentanil pharmacokinetics and metabolism in humans. Anesthesiology 1988; 69: 527534.
Michniewicz BM, Black AE, Sinz MW, et al. In vitro and in vivo metabolism of atorvastatin (CI-981). ISSX Proc 1994; 6: 93.
Ishigami M, Hoda T, Takasaki W, et al. A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on the CYP 3A4-dependent oxidation of mexazolam in vitro. Drug Metab Dispos 2001; 29: 282288.
Bartkowski RR, Goldberg ME, Larijani GE, Boerner T. Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 1989; 46: 99102.
Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998; 87: 190194.
Penon C, Negre I, Ecoffey C, Gross JB, Levron JC, Samii K. Analgesia and ventilatory response to carbon dioxide after intramuscular and epidural alfentanil. Anesth Analg 1988; 67: 313317.
Maltz HC, Balog DL, Cheigh JS. Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Ann Pharmacother 1999; 33: 11761179.
Norman DJ, Illingworth DR, Munson J, Hosenpud J. Myolysis and acute renal failure in a heart-transplant patient receiving lovastatin. N Engl J Med 1988; 318: 4647.


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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