Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zolpidem.
OBJECTIVE
This study compared the pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic (PK/PD) profile of zaleplon, a new pyrazolopyrimidine hypnotic, with those of zolpidem and placebo.


METHODS
This was a double-blind, 5-period crossover study in which healthy volunteers with no history of sleeping disorder were randomized to 10- or 20-mg oral doses of zaleplon, 10- or 20-mg oral doses of zolpidem, or placebo. The pharmacokinetic characteristics of the active drugs were estimated using a noncompartmental method and NONMEM. Pharmacodynamic characteristics were determined using psychophysical tests, including measures of sedation, mood, mental and motor speed, and recent and remote recall. Results of these tests were used to compare the drugs' relative PK/PD profiles.


RESULTS
Ten healthy male and female volunteers, aged 23 to 31 years, took part in the study. The apparent elimination half-life of zaleplon (60.1+/-8.9 min) was significantly shorter than that of zolpidem (124.5+/-37.9 min) (P < 0.001). Zaleplon produced less sedation than zolpidem at the 2 doses studied (P < 0.001). The sedation scores of the zaleplon groups returned to baseline in less time than those of the zolpidem groups (4 vs 8 hours; P < 0.05). Zaleplon had no effect on recent or remote recall, whereas zolpidem had a significant effect on both measures (P < 0.05).


CONCLUSIONS
In this study in 10 young, healthy volunteers, zaleplon was eliminated more rapidly, produced no memory loss, and caused less sedation than zolpidem at the same doses.
Drover
D
D
Department of Anesthesia, Stanford University School of Medicine, California 94305-5640, USA. ddrover@leland.stanford.edu
Lemmens
H
H
Naidu
S
S
Cevallos
W
W
Darwish
M
M
Stanski
D
D
D000081:Acetamides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077334:Zolpidem
D000081:Acetamides; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D000077334:Zolpidem; C085665:zaleplon