Influence of arteriovenous sampling on remifentanil pharmacokinetics and pharmacodynamics.

INTRODUCTION: Remifentanil is a new, short-acting, rapidly metabolized opioid. Because remifentanil is metabolized in blood and tissues by nonspecific esterases, there is a substantial difference between arterial and venous remifentanil concentrations. This difference may greatly affect the estimation of pharmacokinetic and pharmacodynamic parameters.
OBJECTIVES: To assess the effects of sampling site on the pharmacokinetic and pharmacodynamic characteristics of remifentanil.
METHODS: Ten healthy female subjects received intravenous remifentanil at an infusion rate of 3 microg/kg/min for 10 minutes. Serial blood samples were collected during and after drug administration from the radial artery and antecubital vein. A spectral edge measure was derived from the processed electroencephalographic and used as a measure of opioid effect.
RESULTS: Venous concentrations were lower than arterial concentrations during the infusion of remifentanil. Pharmacokinetic parameters estimated from venous and arterial data differed significantly. When arterial concentrations were plotted against electroencephalographic effect, a classic counterclockwise hysteresis loop was observed, indicating a time-lag between changes in concentration and changes in effect. However, concentrations from venous blood produced a clockwise hysteresis loop that would classically suggest the development of acute tolerance.
CONCLUSIONS: If this study had been conducted with venous samples alone, inappropriate conclusions such as acute tolerance could have been inferred. When designing studies to measure the acute time course (ie, non-steady state) of concentration and effect, the potential effects of sampling site on pharmacokinetic and pharmacodynamic characteristics must be carefully considered, particularly when the arteriovenous drug concentration difference is large.