Unraveling heterogeneity of the clinical pharmacogenomic guidelines in oncology practice among major regulatory bodies

Pharmacogenomics (PGx) implementation in clinical practice is steadily increasing. PGx uses genetic information to personalize medication use, which increases medication efficacy and decreases side effects. The availability of clinical PGx guidelines is essential for its implementation in clinical settings. Currently, there are few organizations/associations responsible for releasing those guidelines, including the Clinical Pharmacogenetics Implementation Consortium, Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety and the French National Network of Pharmacogenetics. According to the US FDA, oncology medications are highly correlated to PGx biomarkers. Therefore, summarizing the PGx guidelines for oncology drugs will positively impact the clinical decisions for cancer patients. This review aims to scrutinize side-by-side available clinical PGx guidelines in oncology.

Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100)

Medications or dietary components can affect both the host and the host’s gut microbiota. Changes in the microbiota may influence medication efficacy and interactions. Daikenchuto (TU-100), a herbal medication, comprised of ginger, ginseng, and Japanese pepper, is widely used in Japanese traditional Kampo medicine for intestinal motility and postoperative paralytic ileus. We previously showed in mice that consumption of TU-100 for 4 weeks changed the gut microbiota and increased bioavailability of bacterial ginsenoside metabolites. Since TU-100 is prescribed in humans for months to years, we examined the time- and sex-dependent effects of TU-100 on mouse gut microbiota. Oral administration of 1.5% TU-100 for 24 weeks caused more pronounced changes in gut microbiota in female than in male mice. Changes in both sexes largely reverted to baseline upon TU-100 withdrawal. Effects were time and dose dependent. The microbial profiles reverted to baseline within 4 weeks after withdrawal of 0.75% TU-100 but were sustained after withdrawal of 3% TU-100. In summary, dietary TU-100 changed mouse microbiota in a time-, sex-, and dose-dependent manner. These findings may be taken into consideration when determining optimizing dose for conditions of human health and disease with the consideration of differences in composition and response of the human intestinal microbiota.

Pharmacogenomics: A focus on antidepressants and atypical antipsychotics

The study of pharmacogenomics is rapidly growing, particularly in the field of mental health. Understanding pharmacogenomic principles can be a challenge for many clinicians. Most mental health genomic data concentrates on variability (response, side effects) with antidepressants and atypical antipsychotics. Current pharmacogenomic practice and research primarily focuses on two areas: pharmacodynamics and pharmacokinetics. Based on the current literature, genetic polymorphisms of pharmacodynamics and pharmacokinetics parameters likely influence medication efficacy, therefore affecting the therapeutic benefit. Additionally, certain pharmacodynamic and pharmacokinetic polymorphisms have been linked to an elevated risk of side effects and adverse events with these medications. In this review, specific pharmacodynamic and pharmacokinetic polymorphisms related to antidepressants and atypical antipsychotics will be discussed, as well as the potential clinical effect these genomic abnormalities have within psychiatric care.