Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jun 9:6:122.
doi: 10.3389/fphar.2015.00122. eCollection 2015.

Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy

Manuela Graziani  1 , Robert Nisticò  2
Affiliations
Review

Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy

Manuela Graziani et al. Front Pharmacol. .

Abstract

Gender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain.

Method: We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics (PK) and pharmacodynamics (PD) of methadone.

Results: None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles and Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT-related cardiac arrhythmias in methadone maintenance subjects.

Conclusion: Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women.

Keywords: gender differences; methadone treatment; pharmacodynamics; pharmacokinetics; toxicology.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abi-Gerges N., Philp K., Pollard C., Wakefield I., Hammond T. G., Valentin J. P. (2004). Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes. Fundam. Clin. Pharmacol. 18 139–151. 10.1111/j.1472-8206.2004.00230.x - DOI - PubMed
    1. Bart G., Lenz S., Straka R. J., Brundage R. C. (2014). Ethnic and genetic factors in methadone pharmacokinetics: a population pharmacokinetic study. Drug. Alcohol Depend. 145 185–193. 10.1016/j.drugalcdep.2014.10.014 - DOI - PMC - PubMed
    1. Becker J. B., Hu M. (2008). Sex differences in drug abuse. Front. Neuroendocrinol. 29:47 10.1016/j.yfrne.2007.07.003 - DOI - PMC - PubMed
    1. Berg U. B. (2006). Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors. Nephrol. Dial. Transplant. 21 2577–2582. 10.1093/ndt/gfl227 - DOI - PubMed
    1. Borobia A. M., Novalbos J., Guerra-López P., López-Rodríguez R., Tabares B., Rodríguez V., et al. (2009). Influence of sex and CYP2D6 genotype on mirtazapine disposition, evaluated in Spanish healthy volunteers. Pharmacol. Res. 59 393–398. 10.1016/j.phrs.2009.02.006 - DOI - PubMed

LinkOut - more resources