The Pharmacokinetics of Alfentanil (R39209): A New Opioid Analgesic

Abstract

The pharmacokinetics of alfentanil (R39209), a new short-acting opioid analgesic, were studied in 11 patients. Six patients were given 50 .mu.g/kg alfentanil and 5 patients 125 .mu.g/kg as an i.v. bolus injection. Plasma concentrations were measured at intervals up to 6 h (50 .mu.g/kg) or 8-10 h (125 .mu.g/kg), using a specific radioimmunoassay technique. Plasma concentrations declined triexponentially in both groups. The initial elimination of alfentanil from the plasma was very rapid with 90% of the administered dose leaving the plasma within 30 min. The average half-lives for the 3 phases were similar for both groups. The combined mean (.+-. SEM [standard error of the mean]) half-lives for the 11 patients for the rapid and slow distribution phases were short (t1/2 .pi. = 1.2 .+-. 0.26 min, t1/2.alpha. = 11.6 .+-. 1.63 min). The elimination half-life, t1/2.beta. was 94 .+-. 5.87 min which is considerably shorter than that of other opioids. The mean (.+-. SEM) total body clearance was 6.4 .+-. 1.39 ml.cntdot.kg-1.cntdot.min-1 and the volume of distribution (Vd) was 0.86 .+-. 0.1941/kg. The latter is considerably less than reported values for the chemically related drug, fentanyl, and suggests that alfentanil may have a lower tissue binding affinity than fentanyl. The rapid elimination and short duration of clinical action suggests the feasibility of repeated administration of alfentanil and its use by continuous i.v. infusion.