Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in non-small cell lung cancer patients. To date, no data have been reported about the relationship between nivolumab and VD. The aim of this study was to quantify plasma 25-hydroxyVD (25-VD) and 1,25-VD, nivolumab, and its anti-antibody before starting treatment (baseline) and at 15, 45 and 60 days of therapy. VD-pathway-associated gene single nucleotide polymorphisms (SNPs) were also evaluated. Molecules were quantified through enzyme-linked immunosorbent assay, and SNPs through real-time PCR. Forty-five patients were enrolled. Median nivolumab concentrations were 12.5 μg/mL, 22.3 μg/mL and 27.1 μg/mL at 15, 45 and 60 days respectively. No anti-nivolumab antibodies were found. Correlations were observed between nivolumab concentrations and 25-VD levels. Nivolumab concentrations were affected by VD-pathway-related gene SNPs. VDBP AC/CC genotype and baseline 25-VD < 10 ng/mL predicted a nivolumab concentration cut-off value of <18.7 μg/mL at 15 days, which was associated with tumor progression. This is the first study showing VD marker predictors of nivolumab concentrations in a real-life context of non-small cell lung cancer treatment.
Background:Meropenem is a beta-lactam antibiotic for treating multidrug-resistant gram-negative bacilli infections. The expiry of the drug's patent (Merrem) allowed the production of generics to be commercialized by a few companies, including Hospira and Hikma. The stability of these medicines after reconstitution as reported on a data sheet report is 6 hours for Merrem and 1 hour for generics. Objectives: The aim of this work was to evaluate the stability profile of 3 products in 0.9% sodium chloride until 6 hours. Methods: Six polyolefin bags (2 for each drug, stored in the light and in the dark) were prepared for every test run (n =10) at concentrations of 4 and 10 mg/mL. All solutions were stored at controlled room temperature (25°C ± 3°C) and sampled immediately after preparation and at every hour until 6 hours had passed. The concentrations, pH changes, and the visual clarity were used as stability and compatibility indicators. Results: All 3 drugs retained over 95% of the initial concentration at 3 to 4 hours. At the sixth hour, all the concentrations decayed 8% to 10%. No statistical differences were observed in the percentage deviation values of the stability profile between generics and the branded drug.
Conclusion:The stability profile of the products in polyolefin bags, at 4 and 10 mg/mL, was superimposable during the period of analysis and seems to show small values of deviation (1%-2%). These data do not affect the pharmacokinetics because these variations could be attributed to the intra-and interindividual variability between patients. The products showed the same stability, and consequently they could be used interchangeably in hospital pharmacy.
Technology
A72Eur J Hosp Pharm 2013;20(Suppl 1):A1-A238Materials and Methods Three batches of a 20% (w/v) sterile lidocaine solution were prepared using two sterilisation steps: autoclaving followed by filtration (0.22 µm) inside a horizontal laminar flow hood. Packaging in 10 ml dropping containers prevents intravenous administration and ensures a maximum safe dose (2 g). For physicochemical and microbiological stability studies, samples were stored in the dark at 5 ± 3°C and 22 ± 3°C, for 15 days. Sterility tests and bacterial endotoxins assays were performed (Ph. Eur.). Samples were collected and characterised on days 0 (T0), 7 (T7) and 15 (T15). Colour, odour, appearance, pH, osmolarity, density and lidocaine hydrochloride content were analysed. Results Throughout the study, the 20% (w/v) lidocaine hydrochloride solutions remained clear, colourless, limpid and odourless. The pH of the solutions stored at 5 ± 3°C was 3.6 ± 0.04 (T0), 3.8 ± 0.08 (T7), 3.9 ± 0.02 (T15), and 3.6 ± 0.04 (T0), 3.9 ± 0.02 (T7), 4.0 ± 0.03 (T15) for the solutions maintained at 22 ± 3ºC. The HPLC analyses showed that the lidocaine hydrochloride content was maintained (90-110%) after 15 days in all conditions tested. Density and osmolality remained constant, i.e. 1.0049 ± 0.0036 g/cm 3 and 1175.3 ± 20.2 mOsm/kg, respectively (n = 3). The three batches proved to be sterile and endotoxins-free during the study. Conclusions The lidocaine hydrochloride solution proved to be physicochemically and microbiologically stable for 15 days stored in the dark.No conflict of interest.
Development of pyriDoxal-5-phosphate harD Capsules for paeDiatriC use
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