Abstract
Establishment of rational dosage regimens requires the knowledge of pharmacokinetics and pharmacodynamics in the target population. It has been established that side effects produced by drugs are more frequent in women than in men. This may be due to two possibilities, one is that normalized dose received by women is higher than men and the other is that anatomical and physiological characteristics are a quite different. In this review, some aspects that may play a role in the generation of such differences are analyzed, including the impact on absorption, distribution, metabolism and excretion of drugs. Most of the changes can be explained by differences in volume of distribution and systemic clear- ance, however, presystemic clearance also seems to play a role in such dissimilarities. The final result, in general, is that women have higher plasma levels of drugs and usually these differences are reduced or abolished when data are normalized by the body weight, since both, volume of distribution and systemic clearance are influenced by it; however, there are some cases in which differences remain. Further research oriented to establish the role of each of the ana- tomical and physiological differences in the oral pharmacokinetics of drugs is warranted.
Highlights
During the past decade, pharmacological research has greatly enhanced our understanding of several variables affecting the prescription of medication
The question is this distinction with the man is due to pharmacokinetics and/or pharmacodynamics differences or do females just receive more medication and higher doses than males?, or both actions play a role in these differences
It has been suggested that no significative sex-related difference in the activity and/or content of gastrointestinal CYP3A4 is observed [16,17], and no difference in the bioavailability of drugs due to this pathway is expected; but, on the other hand, in an elegant study carried out with verapamil, it has been demonstrated that presystemic metabolism was, at least partially responseble of the gender differences observed after administration of this drug orally [18]
Summary
Pharmacological research has greatly enhanced our understanding of several variables affecting the prescription of medication. The reasons for this increased risk in female patients are not entirely clear but include gender related differences in pharmacokinetics, pharmacodynamics, immunological and hormonal factors as well as differences in the use of medications by women compared with men. Female has been shown to be a risk factor for clinically relevant adverse drug reactions with a 1.5 to 1.7-fold greater risk of developing an adverse drug reaction compared to male patients [2]. The question is this distinction with the man is due to pharmacokinetics and/or pharmacodynamics differences or do females just receive more medication and higher doses than males?, or both actions play a role in these differences. An analysis about the influence of gender in these factors is carried out
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