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.
Highlights
The most recent statistical data in Europe (EMCDDA, 2014) indicate that females represent roughly one in four drug users entering drug treatment and one in five deaths directly related to drug use
The goal of this review is to supply a selective summary of the literature analyzing pharmacokinetic and pharmacodynamic aspects of M with specific focus on data obtained in women
We reviewed the literature and searched for published articles related to gender differences in opioids pharmacokinetics (PK) and pharmacodynamics (PD)
Summary
The most recent statistical data in Europe (EMCDDA, 2014) indicate that females represent roughly one in four drug users entering drug treatment and one in five deaths directly related to drug use. Gender differences are referred to all phases of natural history of drug abuse, i.e., initiation (Green et al, 2002; Becker and Hu, 2008; Roy et al, 2011; Shand et al, 2011), escalation (Hernandez-Avila et al, 2004), relapse, and treatment retention (Lynch et al, 2002; Greenfield et al, 2007; Niv and Hser, 2007; Kennedy et al, 2013), as well as to adverse effects (Gupta et al, 2007), psychiatric comorbidity (Edokpolo et al, 2010; Sara et al, 2013), and the class of drug of abuse (Simoni-Wastila et al, 2004; Tetrault et al, 2008). In line with data on population of both genders, the 2007 US National Survey on Drug Use and Health indicates that the rate of current heroin use decreased between 2006 and 2007 from 0.06 to 0.02% per cent among females aged 12 or older
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