COMPARATIVE CLINICAL-PHARMACOLOGY OF SHORT-ACTING MU-OPIOIDS IN DRUG-ABUSERS

The clinical pharmacology of fentanyl and alfentanil was examined in o pioid-experienced volunteers with agonist and antagonist sensitivity m easures. Two studies-used within-subject, placebo-controlled, crossove r designs. In study 1, fentanyl (0.125, 0.25 mg/70 kg i.v.) was follow ed at 0, 20, 60 and 180 min by naloxone (10 mg/70 kg i.m.). Agonist ef fects during 180-min and 0-min (control; simultaneous fentanyl-naloxon e i.v. infusion) challenge sessions were-compared. Fentanyl rapidly co nstricted pupils, depressed-respiration and produced subjective ''high '' and opiate symptoms lasting 60 to 120 min, depending on the measure . Naloxone precipitated: withdrawal symptoms of comparable intensity a t each challenge point. In study 2, fentanyl (0.125, 0.25 mg/70 kg i.v .), alfentanil (1, 2 mg/70 kg i.v.) and saline were followed at 1 and 6 hr by naloxone (10 mg/70 kg i.m.). Agonist effects were examined dur ing 6-hr challenge sessions. The two drugs produced a comparable range of effects with similar peak magnitude for 0.125 mg/70 kg fentanyl an d 1 mg/70 kg alfentanil and for 0.25 mg/70 kg fentanyl and 2 mg/70 kg alfentanil. Alfentanil's duration of action was brief (<60 min). Withd rawal was precipitated at 6 hr only after 0.25 mg/70 kg fentanyl. Thes e findings support typical mu opioid characteristics (pleasurable subj ective effects, physical dependence) for both drugs, differential dura tion of action (fentanyl > alfentanil) and peak effects consistent wit h a 1:8 (fefitanyl/alfentanii) potency ratio.