”1 Examining the statement above, we see the phrase “pharmacological function and therapeutic response.” This can be dissected into two major elements: pharmacokinetics and pharmacodynamics. We believe that it is always useful to conceptualize

pharmacology in terms of thinking of what happens to a drug from when it first enters the body to when Inhibitors,research,lifescience,medical it is disposed of (excreted). There are three steps in this trajectory: Drug absorption Drug disposition Drug effect. The first two processes are in the realm of pharmacokinetics, defined as the process by which a drug is absorbed, distributed, metabolized, and eliminated. The proteins involved and the genes that encode them regulate Inhibitors,research,lifescience,medical the velocity and amount of drug that circulates through the body and that enters the target tissue(s). Drug effect, in contrast, is in the realm of pharmacodynamics, which according to Dokoumetzidis at al “is the most complex process during the presence of the drug in the human body. The drug can interact with various physiological systems and thus it is not uncommon for the pharmacodynamic response to be, in reality, nonlinear and governed by mechanisms that have not been studied extensively.”2 Inhibitors,research,lifescience,medical Pharmacogenomics applied to depression – as well as to all other diseases

– faces a major obstacle: how to move from research efforts to widespread clinical use. This has two different elements: First challenge: The Inhibitors,research,lifescience,medical quality and replicability of the research findings. Are

they robust enough to guide clinical practice? Second challenge: The very real gap between robust, universally accepted research findings and changes based on them to clinical guidelines and practice. In the case of major depression, the two challenges above are distributed along the domains of pharmacodynamics Inhibitors,research,lifescience,medical and pharmacokinetics. The first challenge, related to the replicability and robustness of research findings, is applicable to the pharmacodynamic side of Metalloexopeptidase the pharmacogenenomics of depression. The findings on the pharmacokinetic side, in contrast, are for the most part universally accepted, and face the second challenge, which is the grievous gap in translation from solid research to clinical use (Table I). Table I. Pharmacogenomics of depression The genetic basis of drug effects: pharmacodynamics The genetic basis of drug effects is the pharmacodynamic domain of the pharmacogenomics of antidepressants. There has been considerable research in this area, with variable and sometimes Selleckchem BMS777607 contradictory results. As the body of evidence increases, some trends and findings become more solidly established, while other leads turn out to be increasingly harder to confirm.