Background

S-1 (a combination of tegafur, gimeracil, and oteracil) is used to treat various cancers. Bone marrow suppression is a dose-limiting toxicity of S-1. The relationship between relative dose intensity (RDI) and bone marrow suppression has not been investigated. Hence, we aimed to elucidate the threshold for RDI to identify bone marrow suppression induced by S-1.

Methods

In this retrospective cohort study, patients who initiated S-1 treatment at Tokyo Women’s Medical University, Medical Center East between June 2015 and June 2017 were included. Bone marrow suppression induced by S-1 was assessed using Common Terminology Criteria for Adverse Events version 4.0. The relationships between grade 3 or higher bone marrow suppression induced by S-1 and RDIs (i.e., 70, 75, and 80%) were investigated using the multivariate Cox proportional hazard model.

Results

We identified 143 patients in this study. The median RDI was 78.8%. Bone marrow suppression induced by S-1 developed in 19 (13.3%) patients. The multivariate Cox proportional hazard model revealed that grade ≥ 2 lymphocytopenia was associated with bone marrow suppression induced by S-1 regardless of the threshold for RDI. In addition, RDI > 75% [hazard ratio (HR) = 1.71, p < 0.05] and RDI > 80% (HR = 1.65, p < 0.05) were associated with bone marrow suppression induced by S-1.

Conclusions

Reduced dose of S-1 still has the risk of developing bone marrow suppression. Clinicians should assess RDI to identify high risk patients with bone marrow suppression induced by S-1.

Summary

A new rapid, simple, economical, and environment-friendly reversed- phase high-performance thin-layer chromatography (RPHPTLC) method has been established for the simultaneous determination of glycyrrhizin and glabridin in Glycyrrhiza glabra roots, rhizomes and selected herbal formulations. The method was carried out using RP-18 silica gel 60 F_254S HPTLC glass plates and methanol–water (7:3 v/v) as the mobile phase. The developed plates were scanned and quantified densitometrically at 256 and 233 nm for glycyrrhizin and glabridin, respectively. Glycyrrhizin and glabridin peaks from G. glabra roots and rhizomes and herbal formulations were identified by comparing their single spots at R_F = 0.63 ± 0.02 and R_F = 0.28 ± 0.01, respectively. Linear regression analysis revealed a good linear relationship between the peak areas and the amounts of glycyrrhizin and glabridin in the ranges of 1000–7000 and 100–700 ng band⁻¹, respectively. The method was validated, in accordance with the International Conference on Harmonization (ICH) guidelines for precision, accuracy, and robustness. The proposed method will be useful to determine the therapeutic doses of glycyrrhizin and glabridin in herbal formulations as well as in bulk drug.

Background Dose banding (DB) is a strategy to rationalise antineoplastic production at Hospital Pharmacy Aseptic Compounding Units (ACUs) and to reduce patient’s waiting time. DB allows for optimizing workflows and workloads, facilitating adoption of new technologies, and increasing safety, quality and efficiency of the compounding process. Objective To evaluate the potential impact of implementation of Logarithmic DB and to identify antineoplastic agents and preparations that fulfil criteria published and establish the number and standard doses that could be compounded in advance at the ACU. Setting University and Polytechnic third level general hospital. Method Retrospective observational study (December 2015–May 2016). Antineoplastic dose production was analysed. Investigational drugs were excluded. Three criteria were applied following bibliography reviewed to select candidates to be compounded at our ACU as standardised using logarithmic DB: (a) Antineoplastic preparations > 250 per year; (b) psychochemical stability in optimal storage conditions at least 14 days; (c) maximum five logarithmic standardised doses that include at least 60% of all individualised doses compounded for a given drug. Main outcome measure Number of antineoplastic agents, preparations and logarithmic standard doses candidates to DB. Results 15,436 antineoplastic individualised doses corresponding to 69 antineoplastic agents were analysed. At our institution applying selection criteria, 19 (27%) antineoplastic drugs (3 monoclonal antibodies, 16 cytotoxic) were potential candidates to DB. 6285 (40%) of compounded individualised dose preparations could be prepared in 84 logarithmic standard doses in advance. Conclusion Dose banding implementations could contribute to rationalise antineoplastic production and increase the ACUs compounding capacity.

Baicalin was identified as a neuraminidase (NA) inhibitor displaying anti-influenza A virus (IAV) activity. However, its poor solubility in saline has limited its use in the clinic. We generated sodium baicalin and showed that it exhibited greatly increased solubility in saline. Its efficacy against oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) was evaluated in vitro and in vivo. Results showed that 10 μM of sodium baicalin inhibited A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and H1N1-H275Y in MDCK cells in a dose-dependent manner, with inhibitory rates of 83.9, 75.9 and 47.7%, respectively. Intravenous administration of sodium baicalin at 100 mg/kg/d enabled the survival of 20% of H1N1-H275Y-infected mice. The treatment alleviated body weight loss and lung injury. Moreover, sodium baicalin exerted a clear inhibitory effect on NAs. The IC₅₀ values of sodium baicalin against H1N1-H275Y and cells-expressing A/Anhui/1/2013-R294K (H7N9-R294K) NA protein (N9-R294K) were 214.4 μM and 216.3 μM. Direct interactions between sodium baicalin and NA were observed, and we simulated the interactions of sodium baicalin with N9-R294K and N9 near the active sites of OC-N9-R294K and OC-N9. The residues responsible for the sodium baicalin-N9-R294K and sodium baicalin-N9 interactions were the same, confirming that sodium baicalin exerts effects on wild-type and oseltamivir-resistant viral strains.

Background

The aim of this study was to investigate the effect of ellagic acid (EA) on arsenic-induced renal and hepatic toxicity in rats.

Methods

A total number of 35 male Wistar rats were randomly divided into five experimental groups. Group 1 received normal saline (po). Group 2 received sodium arsenite (SA, 10 mg/kg, po) for 21 days. Group 3 received EA (30 mg/kg, po) for 14 days. Groups 4 and 5 received SA 7 days prior to EA (10 and 30 mg/kg respectively) treatment and continued up to 21 days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were measured in kidney and liver.

Results

Treatment with EA (more potently at dose of 30 mg/kg) restored the SA-induced alterations in serum creatinine (Cr) and blood urine nitrogen (BUN) levels as well as the changes in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations (all p < 0.001). Elevated levels of malondialdehyde (MDA) and nitric oxide (NO) in renal and hepatic tissue was reduced by EA treatment (all p < 0.001). Treatment with EA enhanced the glutathione (GSH) content in liver (p < 0.001) and up-regulated renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) mRNA expression (all p < 0.001). The SA-induced histopathological alterations in kidney and liver were reduced by EA treatment.

Conclusion

In conclusion, the presence of EA with SA alleviated its toxic effects and EA treatment might be an effective strategy for the management of arsenic-induced renal and hepatic damage.

Background Knowledge on factors related to preventable medication waste and waste-reducing interventions, including redispensing unused medications, is needed to maximise effectiveness. Objective To assess patient and medication factors associated with preventable medication waste and possibilities for redispensing unused medications. Setting Dutch community pharmacies. Methods In this cross-sectional study, pharmacy-staff registered patient and medication characteristics of prescription medications returned to 41 Dutch community pharmacies during 1 week in 2014. Medications were classified as preventable waste if the remaining amount could have been prevented and as theoretically eligible for redispensing if the package was unopened, undamaged and ≥ 6 months until the expiry date. Associations were analysed using multivariate logistic regression. Main outcome measures Proportion of medications classified as preventable waste and as eligible for redispensing, including factors associated with these medications. Results Overall, 279 persons returned 759 (low-cost) medications, and 39.3% was classified as preventable waste. These medications were more frequently used by men than women (OR; 1.7[1.2–2.3]) and by older (> 65 years) than younger patients (OR; 1.4[1.0–2.0]). Medications dispensed for longer periods were more often unnecessary wasted (1–3 months OR; 1.8[1.1–3.0], > 3 months 3.2[1.5–6.9]). Of all returned medications, 19.1% was eligible for redispensing. These medications were more frequently used by men than women (OR; 1.9[1.3–2.9]). Medications chronically used were more frequently eligible for redispensing than acute use (OR; 2.1[1.0–4.3]), and used for longer periods (1–3 months OR; 4.6[2.3–8.9], > 3 months 7.8[3.3–18.5]). Conclusions Over one-third of waste due to medications returned to community pharmacies can be prevented. One-fifth of returned medications can be redispensed, but this seems less interesting from an economic viewpoint.

We report here the synthesis and our studies of the structure, physicochemical properties, and anticaries activity of a novel potential anticaries substance 2-amino-4,6-dihydroxypyrimidinium hexafluorosilicate. IR spectra, EI mass spectra, and ¹⁹F NMR spectra were obtained and their properties were studied. Biological investigations were performed on animals kept on the Stephan caries-inducing diet (50% sucrose). Alkaline phosphatase (AlkP) and acid phosphatatase (AcP) were assayed in pulp homogenates and the AlkP:AcP ratio was used to assess the mineralization index (MI). AlkP activity was measured in serum, along with alanine aminotransferase (ALT). The number and depth of caries lesions to the teeth were assessed and caries prophylactic efficacy (CPE) was computed. The data showed that 2-amino-4,6-dihydroxypyrimidinium hexafluorosilicate decreased the number of caries lesions by 45.5% and had high anticaries efficacy, five times greater than that of sodium fluoride.

Background A clinical decision support system (CDSS) linked to the computerized physician order entry may help improve prescription appropriateness in inpatients with renal insufficiency. Objective To evaluate the impact on prescription appropriateness of a CDSS prescriber alert for 85 drugs in renal failure patients. Setting Before-after study in a 975-bed academic hospital. Method Prescriptions of patients with renal failure were reviewed during two comparable periods of 6 days each, before and after the implementation of the CDSS (September 2009 and 2010). Main outcome measure The proportion of inappropriate dosages of 85 drugs included in the CDSS was compared in the pre- and post-implementation group. Results Six hundred and fifteen patients were included in the study (301 in pre- and 314 in post-implementation periods). In the pre- and post-implementation period, respectively 2882 and 3485 prescriptions were evaluated, of which 14.9 and 16.6% triggered an alert. Among these, the dosage was inappropriate in respectively 25.4 and 24.6% of prescriptions in the pre- and post-implementation periods (OR 0.97; 95% CI 0.72–1.29). The most frequently involved drugs were paracetamol, perindopril, tramadol and allopurinol. Conclusion The implementation of a CDSS did not significantly reduce the proportion of inappropriate drug dosages in patients with renal failure. Further research is required to investigate the reasons why prescribers override alerts. Collaboration with clinical pharmacists might improve compliance with the CDSS recommendations.