Anna Burkiewicz

JO Olubodun

Maria Gałuszko-Węgielnik

Mariusz Wiglusz

TM Polasek

Wiesław Jerzy Cubała

WJ Cubała

English

PubMed

Springer - Publisher Connector

Zolpidem pharmacokinetics and pharmacodynamics in metabolic interactions involving CYP3A: sex as a differentiating factor

LETTER TO THE EDITORS
Zolpidem pharmacokinetics and pharmacodynamics
in metabolic interactions involving CYP3A:
sex as a differentiating factor
Wiesław Jerzy Cubała & Mariusz Wiglusz &
Anna Burkiewicz & Maria Gałuszko-Węgielnik
Received: 3 May 2010 /Accepted: 28 May 2010 /Published online: 16 June 2010
# The Author(s) 2010. This article is published with open access at Springerlink.com
Keywords Zolpidem . Sex . Pharmacokinetics . CYP3A
To the editor:
We read with interest the recent paper by Polasek et al. on
the evaluation of zolpidem as a mechanism-based inactivator
of human CYP3A in vitro that was accompanied by the
assessment of its metabolic interaction potential with CYP3A
drugs [1]. The article clearly points out the mechanism of
inactivation of human CYP3A in vitro and describes the
implications of this mechanism for the in vivo metabolic
interactions involving CYP3A. Given the prescription rate of
zolpidem, this issue is of vital importance in terms of the
drug’s efficacy and patients’ safety.
However, one issue that was not addressed in the
discussion of this interesting paper is that of the association
between the patient’s sex and the endocrine specificity of
zolpidem—as if zolpidem pharmacokinetics is a gender-
independent factor. Based on current knowledge, the
pharmacokinetics of zolpidem seems to be related to
endocrine factors associated with CYP3A4 metabolism.
As such, low plasma concentrations of free testosterone
may contribute to lower CYP3A activity, with women
achieving up to 50% higher zolpidem plasma levels, while
exposure to testosterone activates the biotransformation via
CYP3A [2]. This effect is conspicuous in the relative higher
incidence of adverse drug reactions with zolpidem in
women [3].
The conclusions of the study reported in the paper are
valid for the model study on male subjects. It would have
been interesting, however, if the discussion were to have
included the exciting element of endocrine-related differ-
ences in zolpidem action.
Conflict of interest statement The authors declare that they have no
conflict of interest.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
References
1. Polasek TM, Sadagopal JS, Elliot DJ, Miners JO (2010) In vitro-in
vivo extrapolation of zolpidem as a perpetrator of metabolic
interactions involving CYP3A. Eur J Clin Pharmacol 66:275–283
2. Olubodun JO, Ochs HR, von Moltke LL, Roubenoff R, Hesse LM,
Harmatz JS, Shader RI, Greenblatt DJ (2003) Pharmacokinetic
properties of zolpidem in elderly and young adults: possible
modulation by testosterone in men. Br J Clin Pharmacol 56:297–304
3. Cubała WJ, Landowski J, Wichowicz HM (2008) Zolpidem abuse,
dependence and withdrawal syndrome: sex as susceptibility factor
for adverse effects. Br J Clin Pharmacol 65:444–445
W. J. Cubała (*) :M. Wiglusz :A. Burkiewicz :
M. Gałuszko-Węgielnik
Department of Psychiatry, Medical University of Gdańsk,
Dębinki 7 St. Build. 25,
80-952 Gdańsk, Poland
e-mail: cubala@gumed.edu.pl
Eur J Clin Pharmacol (2010) 66:955
DOI 10.1007/s00228-010-0854-x


Crossref

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In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A.

Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.

Zolpidem abuse, dependence and withdrawal syndrome: sex as susceptibility factor for adverse effects.

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Zolpidem pharmacokinetics and pharmacodynamics in metabolic interactions involving CYP3A: sex as a differentiating factor

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