This paper is dedicated to the memory of Prof. Dr. med. Hermann R. Ochs, of Soest, Germany, who passed away in 2013 at the age of 69. Over the course of his career he made numerous important research contributions to the medical and scientific literature in the area of clinical pharmacology, including the pharmacologic and pharmacokinetic properties of zolpidem and other benzodiazepine agonists. For nearly four decades he was a valued research colleague and close personal friend of Dr. Greenblatt.
Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration
Version of Record online: 27 NOV 2013
© 2013, The American College of Clinical Pharmacology
The Journal of Clinical Pharmacology
Volume 54, Issue 3, pages 282–290, March 2014
How to Cite
Greenblatt, D. J., Harmatz, J. S., Singh, N. N., Steinberg, F., Roth, T., Moline, M. L., Harris, S. C. and Kapil, R. P. (2014), Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration. Journal of Clinical Pharma, 54: 282–290. doi: 10.1002/jcph.220
- Issue online: 11 FEB 2014
- Version of Record online: 27 NOV 2013
- Accepted manuscript online: 6 NOV 2013 11:25PM EST
- Manuscript Accepted: 28 OCT 2013
- Manuscript Received: 4 SEP 2013
- Transcept Pharmaceuticals, Inc.
- Purdue Pharma L.P
- zolpidem sublingual tablet;
The effect of dose and gender on the pharmacokinetics (PK) and pharmacodynamics (PD) of zolpidem after administration of a buffered zolpidem sublingual tablet (ZST; Intermezzo®, Purdue Pharma L.P., Stamford, CT, USA) was evaluated in healthy non-elderly male and female volunteers. Subjects received a single morning dose of ZST (1.0, 1.75, and 3.5 mg) or placebo in a four-way crossover study. In male and female subjects zolpidem PK were linear, with area under the curve (AUC) proportional to dose, and apparent oral clearance and elimination half-life independent of dose. However, AUC averaged 40% to 50% higher in females than in males receiving the same dose. The gender effect was incompletely explained by body weight. In females, ZST produced PD changes consistent with benzodiazepine agonist effects, particularly at the 3.5-mg dose. For several PD variables, PD effects were significantly related to plasma zolpidem concentrations when data were aggregated across subjects. However, there was variability in response among individuals. In males, PD effects of zolpidem seldom differed from placebo regardless of plasma concentration. The findings confirm that zolpidem clearance is lower in females than in males. PD effects of zolpidem from ZST are greater in female subjects, due to a combination of higher plasma concentrations and greater intrinsic sensitivity.