THE PHARMACOKINETICS OF THE NEW SHORT-ACTING OPIOID REMIFENTANIL (GI87084B) IN HEALTHY ADULT MALE-VOLUNTEERS

Background: Remifentanil (GI87084B) is a new short-acting opioid with a unique ester structure. Metabolism of remifentanil by ester hydrolys is results in very rapid elimination. The aim of this study was to cha racterize in detail the pharmacokinetic profile of remifentanil in hea lthy male volunteers. Methods. Ten healthy adult male volunteers recei ved a zero-order infusion of remifentanil at doses ranging from 1 to 8 mug-kg-1.min-1 for 20 min. Frequent arterial blood samples were drawn and analyzed by gas chromatographic mass spectroscopy to determine th e remifentanil blood concentrations. The raw pharmacokinetic data were analyzed using three different parametric compartmental modeling meth ods (traditional two-stage, naive pooled data, and NONMEM). The raw ph armacokinetic data also were analyzed using numeric deconvolution and a nonparametric moment technique. A computer simulation using the phar macokinetic parameters of the NONMEM compartmental model was performed to provide a more intuitively meaningful and clinically relevant desc ription of the pharmacokinetics. The simulation estimated the time nec essary to achieve a 50% decrease in remifentanil concentration after a variable-length infusion. Results. For each parametric method, a thre e-compartment mamillary model that accurately describes remifentanil's concentration decay curve was constructed. The NONMEM analysis popula tion pharmacokinetic parameters included a central clearance of 2.8 1/ min, a volume of distribution at steady state of 32.8 1, and a termina l half-life of 48 min. The mean results of the nonparametric moment an alysis included a clearance of 2.9 1/min, a volume of distribution at steady state of 31.8 1, and a mean residence time of 10.9 min. The com puter simulation revealed the strikingly unique pharmacokinetic profil e of remifentanil compared to that of the currently available fentanyl family of opioids. Conclusions. Remifentanil is a new, short-acting o pioid with promising clinical potential in anesthesiology.