Sex-Related Differences in Drug Disposition in Man

Abstract

Sex-related differences in the disposition of some analgesics, anxiolytics and hypnotics have recently been reported. With certain benzodiazepines, sex has been shown to be a more important determinant of variability in drug disposition than age, while with other benzodiazepines an age-related decline in clearance was more pronounced in men than women. In young healthy adults these sex-related differences in drug disposition were related to the phase of the menstrual cycle, oral contraceptive steroid administration, and variations in plasma concentrations of albumin, alpha 1-acid glycoprotein, free fatty acids and sex hormones. While none of the sex-related differences so far reported necessitates the modification of a therapeutic dosage regimen, it is prudent that future protocols for pharmacokinetic studies should regard age, sex, the menstrual cycle and oral contraceptive steroids as potential sources of variability.

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

“…Methylprednisolone plasma concentration (C MP ) versus time (t) curves were fitted to the following equation: (1) by use of the nonlinear least-squares regression computer program PCNONLIN (SCI Software Inc., Lexington, Ky.). In equation 1, k f is the first-order rate constant for the formation of methylprednisolone from the methylprednisolone succinate ester, CL represents the clearance of methylprednisolone, and V is the volume of distribution for methylprednisolone.…”

“…Of the studies that have enrolled both men and women, most fail to analyze their findings by gender and instead treat all the subjects as one homogeneous group. 1 This bias in clinical research has been of concern within the health professions. [2][3][4] The literature currently lacks guidelines regarding dosing regimens based on gender.…”

“…Factors that may contribute to a gender-related difference in drug disposition in humans include differences in the ratio of muscle to adipose tissue, hormonal differences (including the menstrual cycle in women), and intrinsic enzyme activity. 1 Corticosteroids are widely used for their antiinflammatory and immunosuppressive effects and represent a class of drugs whose disposition may be influenced by gender. As early as 1958, a gender-related difference in hepatic metabolism of corticosteroids had been noted in rats by Yates et al 10 In humans, two studies have found a 23% and 21% greater clearance of free prednisolone in female compared with male adult subjects.…”

Effect of combined administration of aripiprazole and fluoxetine on cognitive functions in female rats exposed to ethyl alcohol

“…In the absorption phase, differences were observed in release of the medicinal substance due to smaller secretion of gastric acid in women caused by the predominantly alkaline environment (Beirle et al 1999, Robinson 2002). This may result in slower absorption and reduced Cmax (Robinson 2002), in particular in women (regardless of the menstrual cycle phase) (Wilson 1984). Women also show a weaker first pass effect caused by increased CYP2D6 isoenzyme expression (Luzier et al 1999).…”

Annual Review of Chronopharmacology. Volume 7. Biological Rhythms and Medications. Proceedings of the Conference of Chronopharmacology Held in Nice, France on 12-15 March 1990

“…However, the influence of the menstrual cycle on drugs disposition is not well documented, even if among a number of factors which might be expected to contribute to a gender-related differences in drugs pharmacokinetic, the most important factors are thought to be the numerous physiological changes associated to the cyclic variitions in circulating hormone levels that occur during the menstrual cycle. Supporting evidence for this hypothesis has come from a number of studies Wilson, 1984) D-xylose was chosen as a marker for hydrosoluble drugs absorption because it has been used for many years in assessing gastrointestinal absorption in clinical practice.…”