Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA-CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA-CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA-CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA-CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA-CDDP than of free CDDP. SMA-CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg×3 caused a weight loss of more than 5%; SMA-CDDP at 60 mg/kg (CDDP equivalent)×3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA-CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor-selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP.
Multiple-dose ophthalmic preparations that do not contain preservatives carry high risks of microbial contamination. However, there are various types of hospital preparations, with different physicochemical properties. In the present study, we evaluated the association between physicochemical properties and microbial contamination in ophthalmic preparations. The investigated hospital preparations included ophthalmic preparations of physiological saline, 0.2% fluconazole, 0.5% vancomycin hydrochloride, and 2% cyclosporine. We investigated the microbial dynamics of each ophthalmic preparation and microbial contamination in ophthalmic preparations used by patients. Remarkable growth of Pseudomonas aeruginosa, Burkholderia cepacia, and Serratia marcescens was observed in ophthalmic preparations of physiological saline and 0.2% fluconazole. All tested microorganisms displayed decreased counts after inoculation in 0.5% vancomycin hydrochloride. In 2% cyclosporine, all investigated microorganisms were below the limit of detection after inoculation for 6 h. The microbial contamination rates of ophthalmic preparations used by patients were 16.7% (3/18 samples) for 0.5% vancomycin hydrochloride and 0% (0/30 samples) for 2% cyclosporine. All detected contaminants in 0.5% vancomycin hydrochloride were Candida spp., one of which was present at a level of 1 10 4 colony-forming units/mL. The storage method for in-use ophthalmic preparations should be considered on the basis of their physicochemical properties.
Hypoxia‐inducible factor prolyl‐hydroxylase inhibitor (HIF‐PHI) is a novel agent for the treatment of renal anemia. HIF‐PHI increases endogenous erythropoietin production by inhibiting the degradation of an erythropoietin transcription factor. Although beneficial effects are expected from HIF‐PHI, its novel mechanism raises concerns regarding the risk of potential adverse events. The cases of hypothyroidism, which had not been reported in clinical trials, were reported after the administration of roxadustat in a real‐world setting. However, the effects of HIF‐PHIs on thyroid function have not yet been fully evaluated. This study aimed to assess the clinical impact of HIF‐PHIs on thyroid function using the Japanese Adverse Drug Event Report database, a spontaneous reporting system in Japan, because HIF‐PHIs were made available in Japan before they were available in other countries. Although a disproportionality signal for hypothyroidism was detected with roxadustat (reporting odds ratio [ROR]:22.1, 95% confidence interval [CI]:18.3‐26.7, no signals were detected with another HIF‐PHI, daprodustat (ROR:1.3, 95%CI:0.3‐5.4), and epoetin beta pegol (ROR:1.2, 95%CI:0.5‐2.7). Signals of hypothyroidism due to roxadustat were also detected regardless of age or sex. Approximately 50% of hypothyroidism cases were reported within 50 days of starting roxadustat use. These results indicate that roxadustat use may be related to the development of hypothyroidism. The need for monitoring of thyroid function should be alerted during roxadustat administration regardless of age or sex.
The efficacy of biologics in psoriasis treatment is clinically proven; however, biologics are expensive. In this study, we assessed the real‐world cost‐effectiveness of biologics for psoriasis treatment by evaluating the relationship between biologic drug survival (DS) and total medical‐treatment costs from a pharmacoeconomic viewpoint. Furthermore, the effects of patient factors on cost‐effectiveness were investigated. We retrospectively reviewed the medical records of 135 cases who received either a tumor necrosis factor‐alpha (TNF‐α) monoclonal antibody (TNF‐mab), interleukin (IL)‐17 mab, or IL23p19‐mab for psoriasis from January 2010 to June 2020 at Yamaguchi University Hospital. We compared the monthly medical‐treatment costs according to biologic classification and found that costs of medical services, tests, and external preparations required for the treatment process were significantly higher in the TNF‐mab group than in the other groups, and the total medical costs associated with TNF‐mab treatment were significantly higher than those of IL17‐mab treatment. The total monthly cost of medical care was lower in the long‐term DS group than in the short‐term group. The number of prescriptions for external preparations, comprising Vitamin D3 and corticosteroid, was significantly higher in the long‐term DS group than in the short‐term group; in the TNF‐mab group, the proportion of patients without smoking habits was significantly higher in the long‐term group as well. Our study indicated that when costly biologics are used for psoriasis treatment, the maintenance of long‐term DS and appropriate patient guidance might improve the quality of medical care, thus allowing cost‐effective medical care.
Background Eosinophilic pneumonia (EP) is a rare adverse event caused by several types of drugs, such as antibiotics; however, its characteristics remain poorly described. This study aimed to analyze the disproportionality between the occurrence of EP and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents and to characterize anti-MRSA agent-induced EP events using the Food and Drug Administration Adverse Event Reporting System (FAERS). Method Disproportionality linking EP and anti-MRSA agents was analyzed using Bayesian confidence propagation neural networks of information components and reporting odds ratio methodologies. The FAERS dataset for the fourth quarter of 2012 to the fourth quarter of 2022 was used. We also analyzed the characteristics of the case of EP induced by anti-MRSA agents. Results A total of 14,805,795 reports were obtained from FAERS. Disproportionality analysis revealed that the EP signal was detected only in cases with the administration of daptomycin (DAP). This disproportionality signal was consistently detected in the sensitivity analysis. Compared to other reports of DAP-related adverse events, the reports of DAP-related EP were characterized by male sex (odds ratio (OR): 1.94, 95% confidence interval (CI): 1.12–3.37), older age (>70 years; OR: 2.70, 95% CI: 1.68–4.33), and longer duration of treatment (over 21 days; OR: 5.08, 95% CI: 3.21–8.05). Conclusion This study revealed that among the anti-MRSA agents, disproportionality in the occurrence of EP was observed only with DAP. Our results suggest that sex, age, and treatment duration may affect the occurrence of DAP-induced EP. Clinicians should exercise caution regarding EP during DAP administration.
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