Gender differences in the effect of cardiovascular drugs: a position document of the Working Group on Pharmacology and Drug Therapy of the ESC: Figure 1

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in both sexes in developed countries, but gender differences exists in its diagnosis and treatment. Figure 1 Gender differences in absorption and distribution and excretion of drugs responsible for gender differences in pharmacokinetic and pharmacodynamic actions. Since the number of women included in CV studies has often been low, most recommendations in women have often been inferred from effects observed in men.1 This position paper discusses the gaps in knowledge on the effects of gender on pharmacokinetics (PK) and pharmacodynamics (PD) of CV drugs. ### Differences in pharmacokinetics/pharmacodynamics Gender-related differences in PK may arise from differences in body composition, plasma protein binding, metabolizing enzymes and transporters, excretion activity, and/or physiological hormonal changes ( Figure 1 ).2,3 Oral drug absorption is influenced by gastric acid secretion and emptying time, gastrointestinal blood flow and surface area, gut and hepatic metabolism.2,3 Although gender differences in these mechanisms exist, they do not significantly affect drug absorption between the two sexes.2,3 Drug distribution depends on body composition, plasma volume, blood flow, and tissue and plasma protein binding. Women have higher per cent of body fat and lower body weight, plasma volume, and organ blood flow. Increased body fat content explains the faster onset and prolonged duration of action and higher volume of distribution (Vd) of lipophilic drugs, while the Vd of hydrophilic drugs is smaller, producing higher initial plasma levels and greater effects when compared with males.3–5 Plasma and tissue drug concentrations depend on the Vd and clearance (Cl). Exogenous sex hormones increase serum-binding globulins levels.2–5 This effect may be …