Gender differences in drug toxicity.
Clinical data suggest that gender dimorphic profiles are emerging in terms of both drug efficacy and adverse drug reactions (ADRs). With an increasing emphasis on individualised therapies and the need to prevent drug attrition there is a compelling need to understand the molecular basis for gender dimorphic profiles in ADRs and the consequences. Classes of agents exhibiting gender-based variation in pharmaceutical efficacy and toxicity include anaesthetics, HIV-1 therapies and antiarrhythmic drugs. Body weight differences are often cited as a reason for differences in drug pharmacokinetics and subsequent toxicity. However, some studies accounted for these factors and still found significance suggesting that dosage versus body weight does not explain the outcome. Here, we present an overview of current understanding of gender-specific drug toxicity and present rational molecular explanations for these adverse events. There is mounting evidence in support of hormonal effects underpinning the majority of the ADR differences observed between the sexes.
Nicolson
Tamara J
TJ
General Toxicology Sciences, Safety Assessment UK, AstraZeneca R&D, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. Tamara.Nicolson@astrazeneca.com
Mellor
Howard R
HR
Roberts
Ruth R A
RR
D002352:Carrier Proteins / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology*; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012727:Sex Characteristics
D002352:Carrier Proteins; D006728:Hormones; D004364:Pharmaceutical Preparations