The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

The aim of the study was to determine the rate of Potentially Inappropriate Medicines (PIM) and Potential Prescription Omissions (PPO) according to Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment (STOPP/START) criteria. A cross-sectional survey in community pharmacy. A prospective cross-sectional study was performed, during March-May 2012, in five community pharmacies. Patients aged ≥65 years, who collected one or more prescribed medications, were asked to participate in the study, and an interview was scheduled. Patients were asked to provide their complete medical and biochemical record from their general practitioner. 509 patients, mean age 74.8±6.5 years, 57.4% female, participated in the study. 164 PIM were identified in 139 patients (27.3%). The most common were: long-term use of long-acting benzodiazepines (20.7%), use of non-steroidal antiinflammatory drugs (NSAID) in patients with moderate-severe hypertension (20.1%), use of theophylline as monotherapy for chronic obstructive pulmonary disease (COPD, 15.9%) and use of aspirin without appropriate indication (15.2%). Patients with more than four prescpritions had a higher risk for PIM (OR 2.85, 95% CI 1.97–4.14, p<0.001). There were 439 PPO, identified in 257, (50.5%) patients. Predictors for PPO were older age, presence of diabetes, myocardial infarction, osteoporosis, stroke, COPD and/or angina pectoris. STOPP/START criteria may be useful in identifying inappropriate prescribing and improving the current prescribing practices. Pharmacists should focus more on patients with more than four medications and/or patients with gout or pain accompanied with arterial hypertension because those patient may be at higher risk of PIM. Additionlly, patients older than 74 years with diabetes, osteoporosis, myocardial infarction, stroke, angina pectoris and/or COPD may have an increased risk of PPO.

The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.