Clinical Data Combined With Modeling and Simulation Indicate Unchanged Drug-Drug Interaction Magnitudes in the Elderly.

Age-related comorbidities and consequently polypharmacy are highly prevalent in the elderly, resulting in an increased risk for drug-drug interactions (DDIs). The effect of aging on DDI magnitudes is mostly uncertain, leading to missing guidance regarding the clinical DDI management in the elderly. Clinical data obtained in aging people living with HIV ≥ 55 years, who participated in the Swiss HIV Cohort Study, demonstrated unchanged DDI magnitudes with advanced aging for four studied DDI scenarios. These data plus published data for midazolam in the presence of clarithromycin and rifampicin in elderly individuals assessed the predictive potential of the used physiologically-based pharmacokinetic (PBPK) model to simulate DDIs in the elderly. All clinically observed data were generally predicted within the 95% confidence interval of the PBPK simulations. The verified model predicted subsequently the magnitude of 50 DDIs across adulthood (20-99 years) with 42 scenarios being only verified in adults aged 20-50 years in the absence of clinically observed data in the elderly. DDI magnitudes were not impacted by aging regardless of the involved drugs, DDI mechanism, mediators of DDIs, or the sex of the investigated individuals. The prediction of unchanged DDI magnitudes with advanced aging were proofed by 17 published, independent DDIs that were investigated in young and elderly subjects. In conclusion, this study demonstrated by combining clinically observed data with modeling and simulation that aging does not impact DDI magnitudes and thus, clinical management of DDIs can a priori be similar in aging men and women in the absence of severe comorbidities.

The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery.

INTRODUCTION: Nano-scale formulations are being developed to improve the delivery of orally administered medicines, and the interactions between nanoformulations and the gastrointestinal luminal, mucosal and epithelial environment is currently being investigated. The mucosal surface of the gastrointestinal tract is capable of trapping and eliminating large particles and pathogens as part of the natural defences of the body, it is becoming clearer that nanoformulation properties such as particle size, charge, and shape, as well as mucous properties such as viscoelasticity, thickness, density, and turn-over time are all relevant to these interactions. However, progress has been slow to utilise this information to produce effective mucous-penetrating particles. Areas covered: This review focuses on delivery method of nanomedicines both into and across the gastrointestinal mucosal surface, and aims to summarise the biological barriers that exist to successful oral nanomedicine delivery and how these barriers may be investigated and overcome. Expert commentary: Despite successes in the laboratory, no nanotechnology-enabled products are currently in clinical use which either specifically target the intestinal mucous surface or cross the epithelial barrier intact. New nanomedicine-based treatments of local diseases (intestinal cancer, inflammation, infection) and systemic diseases are advancing towards clinical use, and offer genuine opportunities to improve therapy.

Elemental and molecular profiling of licit, illicit, and niche tobacco.

The recognition of differences between regulated large-scale mass manufactured products and the uncontrolled cultivation of tobaccos for illicit purposes plays a significant role within identification of provenance. This research highlights X-ray fluorescence and Fourier transform infrared spectroscopy as useful analytical techniques for the rapid identification of tobacco samples of unknown provenance. Identification of key discriminative features within each technique allowed for the development of typical characteristic profiles for each type of tobacco. Analysis using X-ray fluorescence highlights chlorine, potassium, calcium and iron as key elemental indicators of tobacco provenance. Significant levels of chlorine seen within Snüs samples prompted attempts to visualise chlorine containing regions and structures within the sample. Scanning electron microscopy images showed crystalline structures visible within the Snüs tobacco, structures which Energy dispersive X-ray spectroscopy qualitatively confirmed to contain chlorine. Chloride levels within Snüs samples were quantified using ion chromatography with levels found to range between 0.87mgmL(-1) and 1.28mg. Additionally, FTIR indicated that absorbances attributed to carbonyl stretching at 1050-1150cm(-1), alkane bending at 1350-1480cm(-1) and amide I stretching at 1600-1700cm(-1) highlighting a spectral fingerprint region that allowed for the clear differentiation between different types of tobaccos using PCA analysis, but was limited by differentiation between provenance of cigarettes and hand rolled tobacco. X-ray fluorescence and Fourier transform infrared spectroscopy yielded different information with regards tobacco discrimination and provenance, however both methods overall analysis time and cost reduced indicating usefulness as potential handheld analytical techniques in the field.