Drug Metabolism and Bioanalysis Letters Formerly: Drug Metabolism Letters - Volume 16, Issue 1, 2023

Background: For many years, it was thought that the main function of the colon is the reabsorption of water and salt and the elimination of unused food materials. Only very recently, a crucial role of the human intestinal microbiota in the metabolism of different food constituents, including plant foods-derived flavonoids, was discovered. Currently, the knowledge about colonic degradation of ingested flavonoids, involved bacteria and produced catabolites is rapidly increasing. In general, flavonoids unabsorbed in the small intestine reach the colon, where they are exposed to the gut microbiota. Conclusion: In this perspective article, colonic degradation of flavonoids is considered a reverse process to their biosynthesis in plants, with a special focus on the subclass of flavones. According to this approach: what is composed in plants, will be decomposed in the human colon. Several inverse similarities are highlighted, including hydrolysis of flavonoid glycosides as the first step in the gut degradation contrasted with the attachment of sugar moiety as the last reaction of flavonoid biosynthesis in plants, colonic reduction contrasted with plant introduction of C2-C3 double bond in the central heterocyclic ring, or microbial ring fission contrasted with plant ring closure of the heterocyclic ring of flavones. Despite these inverse similarities, precursors of flavonoid pathway in plants are different from the spectrum of gut microbial catabolites in humans. In the human colon, a wide variety of phenolic acids are produced from the ingested flavonoids, due to the diverse enzymatic capacity of intestinal microbiota. The bioactivities and potential health impacts of these catabolites are still largely unknown.

Risperidone/olanzapine are antipsychotics used in Peru to control symptoms of psychosis. The objective was to review the available evidence on potential pharmacokinetic interactions mediated by CYP1A2 and CYP2D6 polymorphic genes between risperidone or olanzapine and selected drugs for the treatment of COVID-19. A bibliographic search was conducted in SciELO and PubMed/Medline. The selection criteria included all types of articles in English and Spanish languages. In this review, the CYP1A2/CYP2D6/CYP3A4 genes that encode their respective enzymes have been described. The olanzapine/risperidone association increases the risk of prolonging the QT interval; chloroquine/hydroxychloroquine decreases metabolism and increases plasma concentration of risperidone; ritonavir decreases metabolism and increases plasma levels of hydroxychloroquine and lopinavir with the risk of prolonging the QT interval of the cardiac cycle and with a tendency to progression towards Torsades de Pointes. Ritonavir increases metabolism and decreases plasma levels of olanzapine. A low incidence of adverse effect was found between risperidone/azithromycin and olanzapine with azithromycin and hydroxychloroquine. Regarding the association of genes: CYP1A2*1D increases and CYP1A2*1F decreases the plasma concentration of olanzapine. Risperidone plasma levels are increased in CYP2D6 intermediate and poor metabolizers compared with normal metabolizers. Other studies indicate no significant association between poor metabolizers of CYP1A2 and CYP2D6 with increased pharmacokinetic parameters. It is concluded that there are potential risks of prolonging the QT interval due to pharmacokinetic interactions mediated by polymorphic genes CYP1A2 and CYP2D6 between risperidone or olanzapine and the drugs selected for the treatment of COVID-19.

Precision medicine seeks to individualize the dose from the beginning of pharmacological therapy based on the characteristics of each patient, genes involved in the metabolic phenotype, ethnicity or miscegenation, with the purpose to minimize adverse effects and optimize drug efficacy. The objective was to review studies that describe the association of the CYP2D6 and CYP2C19 genes with the tricontinental and Latin American ancestry of Peruvians. A bibliographic search was carried out in PubMed/Medline and SciELO, with various descriptors in Spanish and English. The results of this review confirm that the ethnic origin of Peruvians is tricontinental due to European (mainly Spanish), African and Asian migration, in addition to Latin American migration, being 60.2% mixed, 25.8% Amerindian, 5.9% white, 3.6% African descent, 1.2% Chinese and Japanese descent, and 3.3% unspecified. Studies on CYP2C19*3, CYP2D6*2, *3 and *6 have been reported in Peruvians, and the frequency is similar to that studied in Ecuadorians and Colombians. The CYP2C19*3, CYP2D6*3, and CYP2D6*6 alleles found in Peruvians are common in Europeans, Africans, and Asians; while CYP2D6*4 in Africans and CYP2D6*2 related to Asians. In some studies, the ethnic/gene association has not been demonstrated; while others have shown a significant association, which is why further investigation is warranted. It is concluded that the studies on CYP2D6 and CYP2C19 genes associated with the tricontinental and Latin American ancestry of Peruvians are little, and according to what has been investigated, the CYP2C19*3, CYP2D6*2, *3, *4 and *6 alleles have more related to their ancestry.

Bigels are a novel concept in contrast to previous gel formulations. To look like one gel, bigels are made by merging two gel phases at high shear rates. Colloidal gels can be the same (as in water-in-water bigels, which are phase-separated systems), the same but different, or a combination of a hydrogel and an oleogel. These colloidal gels are utilized to construct bigels (oleogel-in-hydrogel bigels or hydrogel-in-oleogel bigels). Bigels have appealing qualities like hydrophilic and hydrophobic properties, improved spreadability, improved drug penetration, higher stratum corneum hydration, and the capacity to control the drug release rate. Bigels' mechanical, structural, thermal, physical, rheological, and electrical properties are crucial to their practical and successful use in a variety of commercial applications. In this compilation, we have talked about the convenience and interest of bigels as a formulation for novel applications in the pharmaceutical, cosmetic, and food industries. The use of several notable bigels is also discussed in the paper. The Bigels are widely utilized in the food and pharmaceutical industries as well. The Bigels are now being researched as possible drug delivery matrices.

Background: Herbal medicine is widely used in different systems of traditional and complementary medicine. People believe that herbal medicines are safe and more cost-effective than other synthetic medicines. Herbal medicines are also used as a promising source of new drug discovery molecules in modern medicines. Coumarins are polyphenols class phytochemical that naturally occurs in higher plants and are used in medicine for the treatment of human disorders and associated secondary complications. Columbianetin is a coumarin class phytochemical found in Angelica archangelica L. Methods: The aim of the present work is to review the medicinal importance and pharmacological activities of columbianetin and to provide a summary of the medicinal importance and pharmacological activities of columbianetin in medicine. Further scientific progress of columbianetin in the fields of Ethnopharmacology, Phytochemistry and Pharmacology has been analyzed and discussed in the present work. However, possible future research on columbianetin has been also discussed in the present work. Scientific information on columbianetin was collected from PubMed, Elsevier, Google, Google Scholar, and Europe PMC using herbal medicine, columbianetin and coumarin as important keywords. Other published books and journal data have also been included in the present work to know the therapeutic potential of columbianetin in medicine. Results: Scientific data analysis of columbianetin signified the biological importance of phytochemicals belonging to the coumarins. Biological effectiveness of coumarins for their antioxidative, cytotoxic, and anti-inflammatory potential has been discussed in the research fields. Columbianetin has analgesic, antioxidative, anti-inflammatory, anti-proliferative, and anti-allergic activities in medicine. However, its biological effectiveness on neuroprotection, keratinocyte damage and platelet aggregation has also been discussed in the present work. Further tissue distribution of columbianetin in different biological tissue has been estimated through different analytical methods and scientific data are also presented in the present work. Conclusion: The present work summarized the biological importance and pharmacological activities of columbianetin in medicine. Analytical methods developed for the quantitative and qualitative estimation of columbianetin have also been reviewed.

Introduction: This paper aimed to establish a method to help investigate the combination mechanism of traditional Chinese medicine from the metabolic perspective. Background: Semen Strychni has been a frequently used herb in clinics for a long time. In traditional Chinese medical science, Semen Strychni always combinate with other herbs to modulate its nature of severe toxicity. However, the mechanism of the combination is still unclear. Previous research mostly focused on the components of the herbs. The metabolic processes of the main components of the Semen Strychni are also very important and have rarely been reported. Objective: This study tended to develop a rapid and sensitive high-performance liquid chromatographic- tandem mass spectrometric (HPLC-MS/MS) method for the determination of two major metabolites of Semen Strychni in rat urine. Methods: Chromatographic separation was carried out on a C18 column. Detection was performed by a selective reaction monitoring (SRM) mode via an electrospray ionization (ESI) source operating in the positive ionization mode. Analysis of analytes from rat plasma was carried out by protein precipitation using acetonitrile. Results: The assay was validated in terms of specificity, precision, recovery, etc. The intra- and inter-day precision values were less than 13.1%. The recoveries at three levels were more than 69.1%. The method was then used to study the kinetic profiles of the metabolites of Semen Strychni in rat urine for the first time. Conclusion: The results demonstrate that the established LC/MS method in this study is accurate and sensitive for the simultaneous determination of the two metabolites of Semen Strychni in rats' urine samples. This method could be a supplement to the plasma pharmacokinetics of Semen Strychni.

Background: Angiotensin II type 1 (AT 1) receptor antagonist (angiotensin receptor blocker (ARB) called Olmesartan medoxomil (OLM) prevents angiotensin II from acting on the renin-angiotensin-aldosterone pathway, which is a crucial factor in the development of hypertension. OLM is reported to rapidly hydrolyze into its active metabolite, Olmesartan, in plasma after oral treatment. Objective: The objective of the ongoing study was to develop an easy-to-use, precise, and reliable RP-HPLC method for the determination of Olmesartan in bulk as well as pharmaceutical dosage forms. Methods: The stability indicating HPLC method for assay includes the use of Kromasil 100-5-C8 (100 mm × 4.6 mm) column, UV detector 265 nm, and mobile phase composition was a mixture of Acetonitrile: water (70:30) and flow rate of 1.0 mL/min. ICH guidelines were followed in the method's validation. To assess the method's specificity and stability in showing characteristics, stress degradation studies were carried out. The working standard solution of Olmesartan was exposed to 0.1 N HCl at room temperature, 0.1 N NaOH at room temperature, 30 percent hydrogen peroxide by volume, and UV radiation in order to conduct a degradation study. Results: The retention periods of the drug were found to be 1.36 and 1.47 min for standard and sample solutions, respectively. The degradation behaviour of drug under different conditions was studied. The drug was found susceptible to acidic, alkaline and oxidative conditions while it was found stable in photolytic condition. The developed stability-indicating RP-HPLC method for assay was validated as per ICH Q2 guidelines and the validation parameters such as accuracy, precision and specificity were obtained within the accepted criteria. Conclusion: It may be concluded that this method is stability-indicating and specific and can successfully be applied to analyze tablet dosage form containing Olmesartan.