Comparison of potency and duration of action of nalmefene and naloxone.
Nalmefene, a pure opiate antagonist structurally similar to naloxone, possesses a longer duration of action than naloxone at the same dose. However, the relative potency of these two antagonists is not known. This study was, therefore, designed to establish their potency ratio and duration of action at equipotent doses. Sixteen healthy, adult volunteers were allocated to one of four groups of four subjects each. A continuous fentanyl infusion was started to obtain a target plasma concentration of 1.5 ng/mL. The extent of respiratory depression was evaluated at 20 min (first depression) by recording end-tidal CO2 (ETCO2), respiratory rate (RR), arterial oxygen saturation (SpO2), arterial blood gases, and ventilatory response to a hypercapnic challenge. Consecutive groups then received 1, 2, 4, and 8 micrograms/kg of naloxone and nalmefene, in a double-blind, cross-over fashion, on separate occasions. Fentanyl infusion was continued and ETCO2, SpO2, and RR were recorded every 5 min until the values obtained at the first depression were reestablished (second depression). Multiple blood samples for plasma levels of the test drug and fentanyl were taken. Ventilatory function was assessed at baseline, first depression, 5 min after test drug administration, and at second depression. The ventilatory variables were compared using analysis of variance (ANOVA). There was a significant improvement in the slope and intercept of the CO2 response curve produced by the increasing doses (P < 0.05). There was no difference in recovery of these variables between the two drugs at the same dose, implying that the doses were equipotent.(ABSTRACT TRUNCATED AT 250 WORDS)
Glass
P S
PS
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710.
Jhaveri
R M
RM
Smith
L R
LR
D000328:Adult; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009270:Naloxone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors
D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; C038981:nalmefene