Prescription of proton pump inhibitors in older adults with complex polytherapy.

OBJECTIVES: Prescription of proton pump inhibitors (PPIs) may be a source of potentially clinically relevant drug-drug interactions (DDIs) and related complications for elderly patients with complex polytherapy at discharge from hospital. The aim of the study was to identify, through the analysis of hospital discharge records, the co-administrations (PPIs + one or more drugs potentially generating DDIs) hypothetically leading to severe consequences according to the literature and online databases. Subsequently, alternatives to PPIs were evaluated for the treatment of gastric acidity and ulcers. METHODS: The medical records of 1288 patients, discharged from a geriatric ward at the Città della Salute e della Scienza Hospital in Turin from January 2012 to December 2013, were collected in an Excel database for analysis of DDIs using the literature and online sources such as Micromedex. RESULTS : Six hundred and sixty-three of the 1288 clinical folders had a PPI prescription. A list of 18 drugs considered potentially hazardous and able to trigger a DDI when co-administrated with PPIs was drafted; the frequencies of the co-prescriptions of each PPI with one of the listed drugs were esomeprazole 65.38%, lansoprazole 52.87%, omeprazole 48.19% and pantoprazole 37.11%. An analysis of these co-prescriptions, according to Micromedex classification, gave a percentage of major interactions of 11.01% over 663 clinical folders including a PPI. CONCLUSIONS: This study provides a collection of potentially hazardous drug associations and helpful suggestions to improve the quality of prescriptions for elderly patients and strengthens the case for synergic work between doctors and pharmacists in the wards.

New Formulation for the Delivery of Oligonucleotides Using "Clickable" siRNA-Polyisoprenoid-Conjugated Nanoparticles: Application to Cancers Harboring Fusion Oncogenes.

The aim of the present study is to take advantage of the unique property of polyisoprenoid chains to adopt a compact molecular conformation and to use these natural and biocompatible lipids as nanocarriers of drugs to deliver siRNA. A new chemical strategy is applied here to conjugate squalene (SQ) and solanesol (SOLA) to siRNA consisting of an activated variant of the azide-alkyne Huisgen cycloaddition also known as copper-free (Cu-free) click chemistry. We conjugated siRNA against TMPRSS2-ERG, a fusion oncogene found in more than 50% of prostate cancers to SQ or SOLA. First, several parameters such as molar ratio, solvents, temperature, incubation time, and the annealing schedule between both siRNA strands were investigated to bioconjugate the SQ or SOLA via Cu-free click chemistry. The best parameters of the new bioconjugation approach allowed us to (i) increase the synthesis yield up to 95%, (ii) avoid the formation of byproducts during the synthesis, and (iii) improve the reproducibility of the bioconjugation. Then, the biological activity of the resulting nanoparticles was assessed. In vitro, all four formulations were able to decrease the corresponding oncogene and oncoprotein expression. In vivo, only two of the four nanoformulations showed anti-neoplastic activity that seems to be tightly related to their dissimilar biodistribution behavior. In conclusion, we performed a new approach easily transposable for pharmaceutical development to synthesize siRNA-SQ and siRNA-SOLA and to obtain efficient siRNA-nanoparticles. The robustness of the process could be extended to several other polyterpenes and likely applied to other siRNA targeting genes whose overexpression results in the development of cancers or other genetic diseases.