Hostname: page-component-8448b6f56d-tj2md Total loading time: 0 Render date: 2024-04-23T14:07:27.169Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Erikssen J, Madsen S. Treatment of hypercholes- terolemia with statins. Tidsskr Nor Laegeforen 1997; 117: 3216–3220.Google Scholar
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: 1191–1199.Google Scholar
Chang GWM, Kam PCA. The physiological and pharmacological roles of cytochrome P450 isoenzymes. Anaesthesia 1999; 54: 42–50.Google Scholar
Nelson DR, Koymans L, Kamtaki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6: 1–42.Google Scholar
Segaert MF, De Soete C, Vandwiele I, Verbanck J. Drug interaction-induced rhabdomyolysis. Nephrol Dial Transplant 1996; 11: 1846–1847.Google Scholar
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: 1613–1619.Google Scholar
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: 490–496.Google Scholar
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: 311–312.Google Scholar
Meistelman C, Saint-Maurice C, Lepaul M. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987; 66: 13–16.Google Scholar
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: 36–50.Google Scholar
Meuldermans W, Van Peer A, Hendrickx J, et al. Alfentanil pharmacokinetics and metabolism in humans. Anesthesiology 1988; 69: 527–534.Google Scholar
Michniewicz BM, Black AE, Sinz MW, et al. In vitro and in vivo metabolism of atorvastatin (CI-981). ISSX Proc 1994; 6: 93.Google Scholar
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: 282–288.Google Scholar
Bartkowski RR, Goldberg ME, Larijani GE, Boerner T. Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 1989; 46: 99–102.Google Scholar
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: 190–194.Google Scholar
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: 313–317.Google Scholar
Maltz HC, Balog DL, Cheigh JS. Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Ann Pharmacother 1999; 33: 1176–1179.Google Scholar
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: 46–47.Google Scholar