Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents

Abstract

Gender is an important risk factor for adverse drug reactions. Women report significantly more adverse drug reactions than men. There is a growing consensus that gender differences in drug PK is a main contributor to higher drug toxicity in women. These differences stem from physiological differences (body composition, plasma protein concentrations, and liver and kidney function), drug interactions, and comorbidities. Contrast agents are widely used to enhance diagnostic performance in computed tomography and magnetic resonance imaging. Despite their broad use, these contrast agents can lead to important adverse reactions including hypersensitivity reactions, nephropathy, and hyperthyroidism. Importantly, female gender is one of the main risk factors for contrast agent toxicity. As these adverse reactions may be related to gender differences in PK, this perspective aims to describe distribution and elimination pathways of commonly used contrast agents and to critically discuss gender differences in these processes.

Elucidating Gender-Specific Distribution of Imipramine, Chloroquine, and Their Metabolites in Mice Kidney Tissues through AP-MALDI-MSI

“…There is an increasing agreement that gender-specific differences in drug pharmacokinetics are a major factor contributing to higher drug toxicity in females. These variations arise from physiological differences such as body composition variations, plasma protein concentrations, and liver and kidney function [35]. Kidneys are frequently involved in the detoxification process by being exposed to drugs and their metabolites in the bloodstream; drug-induced nephrotoxicity in the kidney is a common, widespread clinical concern [36,37].…”

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

“…The omission of females from preclinical research was motivated by concerns among researchers about potential variations induced by the estrus cycle, along with apprehensions about increased costs [8,9]. However, since hormonal differences play an important role not only in the development of diseases such as anxiety and depression, asthma, and inflammatory bowel disease but also in pharmacokinetics, it was important to establish guidelines that define sex as a biological variable [10][11][12][13][14]. Therefore, in 2016, the Association of Science Editors published the SAGER guidelines (Sex and Gender Equity in Research), which regulate reporting on sex and gender in scientific publications [2,15].…”