84 To summarize, multiple confounds (ethnic and age effects, smoking, body size, multiple enzymatic processing of probes, small sample sizes, etc) notwithstanding, it appears that the activity of CYP3A4 and CYP2D6 are increased in women, CYP1A2 activity is increased in men, and CY.P2C9 and CYP2C19 are unaffected by sex. Elimination Following metabolic transformation, drugs arc eliminated from the body via the kidneys. A few studies found lower GFR and renal blood flow in women,85,86 although the authors noted that this sex difference can Inhibitors,research,lifescience,medical be partly explained by increased muscle mass in men. Other researchers found no sex differences in
GFR and renal blood flow,87 including two studies that MLN8237 mw controlled for weight differences.88,89 Nonetheless, the data, appear to suggest slightly elevated renal
function in males, leading Inhibitors,research,lifescience,medical to increased renal secretion of drugs. In short, the myriad factors affecting drug kinetics in the body make it impossible to come to any simple conclusions about sex and pharmacokinetics and, more importantly, about the effects of sex on drug plasma levels and efficacy. Pharmacokinetics of psychotropic medications While sex can affect virtually any aspect, of medication processing, there is surprisingly little evidence that, sex has a major impact on Inhibitors,research,lifescience,medical actual blood levels of most, psychotropic drugs. What follows is a summary of studied sex effects for benzodiazepines, antidepressants, and antipsychotics. Benzodiazepines Despite several examples of increased benzodiazepine absorption in women, almost all studies of benzodiazepine pharmacokinetics found no sex differences Inhibitors,research,lifescience,medical in absorption.90-100 It. appears, then, that Inhibitors,research,lifescience,medical sex has little, if any, influence on the absorption of benzodiazepines and is not. of general clinical, relevance. With distribution, the results are less clear as to whether a sex difference exists. Benzodiazepines are highly lipophilic drugs and are, therefore, preferably distributed in adipose tissue. As such,
observed sex differences in drug distribution are thought to be the result, of sex differences in body composition. Nonetheless, the majority of studies on benzodiazepine pharmacokinetics reveal no sex differences in distribution.90-92,94,99,101-107 The most, notable exception to this observation almost is diazepam, studies of which have consistently found increased volume of distribution in women.96,97,108 Apart, from diazepam, then, sex and reproductive steroids, both exogenous and endogenous, have little effect, on the distribution of benzodiazepines. While elimination was clearly not sexually dimorphic for many benzodiazepines, several studies showed mixed results, with some researchers finding sex differences in elimination rates for a particular medication and other researchers finding none.