PHARMACOKINETICS OF ALFENTANIL DURING AND AFTER A FIXED RATE INFUSION

Most information on the pharmacokinetics of alfentanil has been obtained after a single bolus injection in patients under general anaesthesia [1-7]. Maitre [8] used data from four of those studies to calculate a set of average population pharmacokinetic parameters for alfentanil after a bolus injection, using the NONMEM computer program [9,10]. Sex, body weight and particularly age were noted to be factors affecting the dis-position of alfentanil in the normal population of surgical patients without liver or renal function impairment. There are only a few detailed pharmacokinetic studies of a continuous infusion of alfentanil, despite the clinical importance of this technique [11—13]. Both Fragen and colleagues [11] and Shafter, Sung and White [12] used a two-compartment model in their kinetic analysis, whereas Reitz and co-workers [13] applied a model-independent approach. The pharmaco-kinetic parameters for alfentanil given by i.v. infusion were similar to those after a single bolus injection, but there were also some conflicting data. Based on a diminished clearance found in two of 11 patients, Reitz [13] claimed that the clearance of alfentanil decreased linearly with duration of infusion. In contrast, Shafer [12] did not find such a correlation. These conflicting findings may be a result of the small numbers of patients included in these studies. Only a few subjects older than 60 yr were included. We have therefore investigated a larger population, using infusions of longer duration