Mk. Greenwald et al., COMPARATIVE CLINICAL-PHARMACOLOGY OF SHORT-ACTING MU-OPIOIDS IN DRUG-ABUSERS, The Journal of pharmacology and experimental therapeutics, 277(3), 1996, pp. 1228-1236
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.