Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics : an UNGAP review

The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clinical evidence for the impact of some of these factors on drug pharmacokinetic variability is mounting: e.g. gastric pH and emptying time, small intestinal fluid properties, differences in pediatrics and the elderly, and surgical changes in gastrointestinal anatomy. However, the link of colonic factors variability (transit time, fluid composition, microbiome), sex differences (male vs. female) and gut-related diseases (chronic constipation, anorexia and cachexia) to drug absorption variability has not been firmly established yet. At the same time, a way to decrease oral drug pharmacokinetic variability is provided by the pharmaceutical industry: clinical evidence suggests that formulation approaches employed during drug development can decrease the variability in oral exposure. This review outlines the main drivers of oral drug exposure variability and potential approaches to overcome them, while highlighting existing knowledge gaps and guiding future studies in this area

TYPE 2 DIABETES MELLITUS AND ITS VASCULAR COMPLICATIONS

Type 2 diabetes mellitus (T2DM) is marked by increased morbidity and mortality because of its effects on the vascular system, which are both direct and indirect. Microvasculopathy is primarily caused by hyperglycemia. Various organ systems are damaged and fail as a result of T2DM and its complications. There are two types of adverse effects of hyperglycemia: macrovascular complications and microvascular complications. It is very important that physicians understand the relationship between diabetes and vascular disease because diabetes prevalence is increasing in the India, and the clinical arsenal for first and secondary prevention of these complications is expanding</jats:p

Sexual Dimorphism in Drug Metabolism and Pharmacokinetics

Background:Sex and gender-based differences are observed well beyond the sex organs and affect several physiological and biochemical processes involved in the metabolism of drug molecules. It is essential to understand not only the sex and gender-based differences in the metabolism of the drug but also the molecular mechanisms involved in the regulation of drug metabolism for avoiding sex-related adverse effects of drugs in the human.Method:The articles on the sex and gender-based differences in the metabolism of drug molecules were retrieved from the Pub Med database. The articles were classified into the metabolism of the drug molecule, gene expression regulation of drug-metabolizing enzymes, the effect of sex hormones on the metabolism of drug, expression of drugmetabolizing enzymes, etc.Result:Several drug molecules are known, which are metabolized differently in males and females. These differences in metabolism may be due to the genomic and non-genomic action of sex hormones. Several other drug molecules still require further evaluation at the molecular level regarding the sex and gender-based differences in their metabolism. Attention is also required at the effect of signaling cascades associated with the metabolism of drug molecules.Conclusion:Sex and gender-based differences in the metabolism of drugs exist at various levels and it may be due to the genomic and non-genomic action of sex hormones. Detailed understanding of the effect of sex and related condition on the metabolism of drug molecules will help clinicians to determine the effective therapeutic doses of drugs dependingon the condition of patient and disease.</jats:sec

SOD, GR, GPX AND GSH ACTIVITY IN DIABETIC RETINOPATHY OF TYPE 2DIABETES IN WESTERN POPULATION OF GUJARAT

Prolong period of hyperglycemia in type 2 diabetes mellitus (T2DM) has been shown to increase the production of oxygen free radicals. T2DM complications such as diabetic retinopathy (DR) can be aggravated by hyperglycemia, which stimulates oxidative stress. The purpose of the study is to find out the status of superoxide dismutase (SOD), glutathione (GSH), glutathione reductase (GR), and glutathione peroxidase (GPx) in healthy, T2DM and DR group.</jats:p

Case report: dual diagnosis of Mulibrey nanism and Jacobs syndrome in an Indian boy

Abstract Background Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome caused by TRIM37 gene variants characterized by growth failure, dysmorphic features and congestive heart failure. We report a 6-year-old boy with Mulibrey nanism and Jacobs syndrome who was referred to us on suspicion of some genetic syndrome. Case description A 6-year-old boy was referred for genetic evaluation with a suspected diagnosis of Silver-Russell syndrome. Comprehensive genetic analysis of the proband was conducted using both classical and modern techniques, including karyotyping, chromosomal microarray (CMA), and whole exome sequencing (WES). G-banding chromosomal analysis revealed a mosaic pattern of 47,XYY[25]/46,XY[25], indicative of Jacobs syndrome. Further analysis with CMA identified a pathogenic mosaic gain of Y chromosome consistent with the karyotype results; no other pathogenic copy number variants were observed. Finally, WES revealed a nonsense homozygous variant c.586C > T in the TRIM37 gene which is causative of Mulibrey nanism. Conclusion This case marks the first documented instance in India of the co-occurrence of Mulibrey nanism and Jacobs syndrome, adding significant insights into the genetic diversity and clinical presentation of these conditions. The study highlights the importance of various genetic tests to diagnose rare genetic syndromes with overlapping phenotype