Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Approach.

Nanomedicines are nanoparticle-based therapeutic or diagnostic agents designed for targeted delivery or enhanced stability. Nanotechnology has been successfully employed to develop various drug formulations with improved pharmacokinetic characteristics, and current research efforts are focused on the development of new innovator and generic nanomedicines. Nanomedicines, which are often denoted as complex or nonbiological complex drugs, have inherently different physicochemical and pharmacokinetic properties than conventional small molecule drugs. The tools necessary to fully evaluate nanomedicines in clinical settings are limited, which can hamper their development. One of the most successful families of nanomedicines are iron-carbohydrate nanoparticles, which are administered intravenously (IV) to treat iron-deficiency anemia. In the U.S., the FDA has approved six distinct iron-carbohydrate nanoparticles but only one generic version (sodium ferric gluconate for Ferrlecit). There is significant interest in approving additional generic iron-carbohydrate drugs; however, the lack of a direct method to monitor the fate of the iron nanoparticles in clinical samples has impeded this approval. Herein we report a novel liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) method that allows for the direct quantification of the iron-carbohydrate drugs in clinical samples, while simultaneously measuring the speciation of the iron released from the nanoparticles in biological samples. To our knowledge, this is the first time that iron nanoparticles have been observed in clinical samples, opening the door for direct pharmacokinetic studies of this family of drugs. This method has potential applications not only for iron-nanoparticle drugs but also for any nanomedicine with an inorganic component.

The Cost of Self-Reported Penicillin Allergy: A Systematic Review.

BACKGROUND: Patients who report a penicillin (PCN) allergy receive suboptimal antibiotic therapy compared with patients not reporting an allergy. However, a majority of patients who report PCN allergy are not truly allergic on confirmatory testing. Ruling out PCN allergy by testing may improve clinical and economic outcomes for patients with reported allergies requiring antibiotic therapy. OBJECTIVE: The objective of this study was to summarize clinical and economic outcomes associated with PCN allergy and provide recommendations for future cost-effectiveness analyses for PCN allergy testing. METHODS: A literature search was conducted using SCOPUS, EMBASE, and PubMed, including all articles published any date through April 25, 2017 (PROSPERO Registration number 42017064112). A total of 1518 abstracts were found during the initial search with 96 duplicates, for a total of 1422 articles for screening. Thirty articles were included for qualitative synthesis and full data extraction. RESULTS: The majority of the studies included had an observational design focusing on inpatient admissions. The most frequently measured outcome in the context of PCN allergy was optimizing antibiotic therapy. Patients with PCN allergy were found to have direct drug costs during inpatient admission ranging from no difference to an additional $609/patient compared with patients without PCN allergy. Outpatient prescription costs were estimated from $14 to $193/patient higher for PCN allergic patients. Total inpatient costs were less for patients without PCN allergy with average savings from $1145 to $4254/patient. CONCLUSIONS: Evaluations of clinical and economic outcomes of PCN allergy are primarily observational and focus on inpatient populations. Long-term relationships between PCN allergy and clinical and economic outcomes are unknown.