Comparative abuse liability of intravenously administered remifentanil andfentanyl

Remifentanil is a short-acting, esterase-metabolized opioid analgesic. This study compared the abuse Liability of remifentanil with that of fentanyl a nd placebo in a randomized, double-blind, crossover study. Twelve recreatio nal users of opioids received increasing doses of remifentanil (0.6, 1.2, 1 .8, 2.4, and 3.0 mug/kg), fentanyl (0.4, 0.8, 1.3, 2.0, 3.0, and 4.5 mug/kg ) and placebo via an intravenous infusion pump. Subjective measures (Cole/A ddiction Research Center Inventory [ARCI] scales and visual analog scale [V AS] items such as "High" and "Good Effects") and physiologic variables (blo od pressure, O-2 saturation, pupil diameter) were recorded. For each measur e, the differences from baseline were reduced to an area under the response curve (AUC) and a peak, and each subject's response to the maximum tolerab le dose for each of the two active drug classes and mean response to severa l placebo infusions were entered into a 12 x 3 analysis of variance. All di fferences in drug versus placebo effects were significant. Although a major ity of the peak effects that were measurable within 4 minutes after drug in fusion reflected greater remifentanil effects, only one, High VAS, was stat istically significant. In contrast, observations that could only be made gr eater than or equal to5 minutes after drug infusion predominantly indicated significantly greater fentanyl peak effects, including High VAS, Liking VA S, Good Effects VAS, and Cole/ARCI Abuse Potential. Fentanyl AUCs were gene rally significantly larger than the corresponding remifentanil AUCs. A drug abuser seeking longer-lasting drug effects might select fentanyl over remi fentanil, but these data do not completely rule out remifentanil abuse by s ome individuals with access to both the drug and the infusion equipment or by those who prefer briefer, repeated effects.