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.

Summary

Ion channels regulate a diversity of physiological functions such as neuronal signalling, cardiac excitability and immune cell response. All of these systems may be affected during the conduct of general as well as local anaesthesia. Thus, the investigation of anaesthetic action on ion channels has become the focus of an increasing number of laboratory studies. Consequently, the concepts of ion channel physiology are becoming important for understanding the scientific and pharmacological basis of clinical anaesthesia. This brief guide is intended to help in understanding the increasing number of studies concerned with the effects of anaesthetic agents on ionic currents. The generation of ionic currents requires a complex molecular interplay of ions, ion channel proteins and lipid membranes. Anaesthetic agents frequently exhibit more than a single effect on ion channel function. Their effects can be described by quantifying the pharmacological alteration of ion channel activation, conductance and inactivation. Many physiological functions are directly influenced by ion channels. Pharmacological action on ion channels is thus fundamental to effects as well as side-effects of anaesthetic agents. The alteration of ion channel function by anaesthetic agents consequently determines their clinical effects.