Annotated BibliographyThis article examined the effect of several agents that could potentially impact the pharmacokinetic parameters of vortioxetine.
The effect of inhibitors and an inducer of the various CYP involved in the metabolism of vortioxetine was studied. Also, the effect of selected CYP substrates on vortioxetine that were likely to be co-administered with this antidepressant was also studied. The co-administered agents selected was ketoconazole, fluconazole, ethinyl estradiol/levonorgestrel, bupropion, rifampicin and omeprazole. Based on the results from the tests it was concluded that a lower dose of vortioxetine should be considered in major depressive disorder patients if they are co-administered either rifampicin or bupropion. This article discussed vortioxetine pharmacokinetics and its potential drug interactions. Vortioxetine was discovered to have a pharmacokinetic profile that was favorable with, dose-proportional, oral bioavailability and a long half-life.
Other factors such as its absorption, distribution, metabolism an elimination was discussed in relation to pharmacokinetics. Intrinsic factors such as sex, race/ethnicity, age, body size and hepatic/renal impairment was analyzed and none of these factors affected exposure to vortioxetine. Its drug interactions were studied for how vortioxetine impacts other drugs and how other drugs may impact vortioxetine. Lastly clinical pharmacodynamics for phase I was studied. This studied things such as the effect of vortioxetine on neurotransmitters and the effect of vortioxetine of cognitive function.This article showed that vortioxetine has an effective initial and maintenance treatment for major depressive disorder. The factors of Major depressive disorder and symptoms of depression was the first this discussed.
The essentials of vortioxetine such as its chemical properties, drug interactions, and mechanism of actions were discussed. Vortioxetine displayed adverse effect like other drugs on the market. There were several Side effects that were shown to be more bearable and side effects that showed increased based on data from previous clinical trials. This article reviewed the pharmacological profile, available efficacy and tolerability/safety data on vortioxetine. Its pharmacological profile reviewed vortioxetine chemistry, pharmacodynamics, pharmacokinetics and metabolism. Its clinical efficacy was on individual studies for acute treatment of major depression, pooled data analyses from acute-phase studies, and longer-term treatment of major depression. Short term-studies showed that there was a great reduction in depression symptoms with vortioxetine in varying number of different doses in comparison to the placebo.
Vortioxetine appeared to be well tolerated and have low incidence effects on adverse effects for sexual functioning for the pooled data analyses. There were no previous studies that showed that vortioxetine was more effective than other types of antidepressants. This article deciphered the molecular basis for high affinity binding of vortioxetine in human serotonin transporter. A combination of computational, chemical and biological methods was used to decipher it.
Vortioxetine showed to adopt several distinct binding modes within the central binding site of human serotonin transporter. An experimentally validated model of the relevant binding mode of vortioxetine in the human serotonin transporter was generated. This was completed by using comparative modeling and mutational analysis/characterization of drug analogs binding to selected point mutants. The findings from this article provided a platform for designing novel multimodal drug with tailor-made activity with several 5-HT proteins and was essential for future structure-based drug discovery.