Biologic and Molecular Mechanisms for Sex Differences in Pharmacokinetics, Pharmacodynamics and Pharmacogenetics: Part II

Abstract

There are specific pharmacology issues related to women's unique physiology, including the hormonal changes that occur throughout their life span. Studies have shown alterations in drug metabolism in relation to phase of menstrual cycle, during pregnancy, or after menopause. In the brain, hormones can alter the response to drugs through various mechanisms. Estrogen and other compounds can bind to the estrogen receptor and modulate a wide range of activities within the cell. In addition, animal studies have demonstrated sexual dimorphism in the brain in terms of both the type of response to estrogen and the response as related to timing of administration. Many normal physiological changes that occur during pregnancy can affect pharmacokinetics and pharmacodynamics. These changes during pregnancy are dramatic rises in levels of estrogen and progesterone, increases in maternal blood volume, altered protein binding resulting from a drop in albumin levels, and a rise in levels of other plasma proteins. The field of chronobiology offers a way to study these changes in biological functions. Chronopharmacology is the study of how biological rhythms, particularly 24-hour, menstrual cycle, and annual rhythms, impact the pharmacokinetics and pharmacodynamics of drugs as a function of their timing. Chronopharmacokinetics is the study of the absorption, distribution, metabolism, and elimination of medicines according to the time of day, menstrual cycle, or year. In addition to applying chronobiology to the study of drugs used in women, new technologies were addressed from computer modeling, pharmacogenetics (genetics of the response to drugs), and in vivo drug metabolism studies.

Effects of Menstrual Cycle on Postoperative Analgesic Requirements, Agitation, Incidence of Nausea and Vomiting after Gynecological Laparoscopy

“…Studies have shown alterations in drug metabolism in relation to the phase of the menstrual cycle, during pregnancy, or after menopause [18]. No previous study has investigated the effect of the menstrual cycle on metamizol consumption after gynecological laparoscopy.…”

Intrahippocampal muscimol shifts learning strategy in gonadally intact young adult female rats

“…4) and we may be unable to detect further strategy shifts. It is also possible that the different effects of muscimol treatment on strategy use across the estrous cycle relate to differences in drug metabolism (for review, see Anthony and Berg 2002). To tease apart these possibilities, we are currently testing strategy shifts to place in rats at estrus following challenge with GABA A antagonists such as bicuculline.…”

Pharmacogenomics of multigenic diseases: Sex-specific differences in disease and treatment outcome

“…4,5 Also, drug metabolism-related differences have been reported, as a function of life cycle, particularly in females going through puberty or menopause. 6,7 Here we wish to address the question of how genetic factors contribute to disease susceptibility and drug response in complex disorders that are known to vary considerably in male and female patients. We have selected coronary artery disease, depression, and schizophrenia, because a rich literature already exists on the etiology of these diseases, and sex differences are prominent but still poorly understood.…”