Elimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin.
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.
McDonnell
C G
CG
Cork University Hospital, Department of Anaesthesia and Intensive Care Medicine, Wilton, Cork, Ireland. conormcdonnell@hotmail.com
Malkan
D
D
Van Pelt
F D
FD
Shorten
G D
GD
D000328:Adult; D000368:Aged; D015760:Alfentanil / Q000097:blood / Q000493:pharmacokinetics*; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D000069059:Atorvastatin; D002849:Chromatography, Gas; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000701:Analgesics, Opioid; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D015760:Alfentanil; D000069059:Atorvastatin