PREDICTIVE ACCURACY OF CONTINUOUS ALFENTANIL INFUSION IN VOLUNTEERS -VARIABILITY OF DIFFERENT PHARMACOKINETIC SETS

To evaluate the variability of the predictive accuracy of alfentanil b y using different pharmacokinetic data sets, eight healthy young male adult volunteers were given the same alfentanil infusion for 4 h. Nine teen venous blood samples were taken from each volunteer, and alfentan il concentrations were titrated by radioimmunoassay For each volunteer , the pharmacokinetic variables of a two-compartment model were calcul ated, averaged, and considered as a reference set. Based on the infusi on profile given to the volunteers, central compartment concentrations were calculated by using the reference set and nine previously publis hed pharmacokinetic sets of alfentanil concentrations in healthy adult s. The bias, inaccuracy, and dispersion of each data set were assessed by determining the median performance error, the median absolute perf ormance error (MDAPE) and the 10th and 90th percentiles, respectively. By using the pharmacokinetic variables of the volunteers, the predict ive accuracy was excellent (MDAPE, 7.25%). Among the 10 averaged pharm acokinetic sets, there was a significant correlation between their bia s and clearance (R2 = 0.996). The reference set had the best predictiv e accuracy (MDAPE, 23.6%). Five sets from the literature also showed a reliable predictive accuracy but four other sets with a clearance mor e than 5 mL.kg-1-min-1 and derived from a large bolus injection were i naccurate (MDAPE >50%) as they underestimated the alfentanil concentra tions. We conclude that pharmacokinetic sets derived from large bolus should not be selected to accurately predict alfentanil infusion.