Pharmazie最新文献

Enteral nutrients (ENs) affect the plasma drug concentration of orally co-administered drugs, particularly those of antiepileptic drugs, such as phenytoin and carbamazepine. However, few studies have reported the interactions of levetiracetam (LEV), an upcoming antiepileptic drug, with ENs. In this study we aimed to investigate the pharmacokinetics of LEV in 55 rats after oral co-administration of LEV with liquid or semisolid ENs. Compared with the control group, co-administration with Terumeal ® Soft significantly decreased the plasma LEV concentration at 0.5, 1, and 2 h and area under the plasma concentration-time curve from 0 to 3 h (AUC_0→3h) (P < 0.01). However, the AUC_0→3h of LEV remained unchanged following the administration of Terumeal ® Soft 2 h after the initial LEV administration. Moreover, co-administration with semisolid Racol® NF delayed the absorption of LEV without decreasing the AUC_0→3h, whereas liquid Racol ® NF did not alter LEV pharmacokinetics. Thus, co-administration of LEV with Terumeal® Soft reduced the absorption of LEV from the gastrointestinal tract, which was prevented by administering Terumeal ® Soft 2 h after LEV administration. Semisolid Racol ® NF altered LEV pharmacokinetics without decreasing its gastrointestinal absorption. Our findings suggested that careful monitoring of the plasma LEV levels is necessary when co-administering LEV with Terumeal ® Soft, semisolid Racol ® NF, or any other semisolid ENs, to prevent the inadvertent effects of the interaction between LEV and ENs.

Background and aim: Drug-related problems (DRP) jeopardize patient safety. Unit-dose dispensing systems (UDDS) with computerized-physician-order-entry (CPOE) and clinical-decision-support-systems (CDSS) were reported as a promising concept for preventing DRP. We aimed at identifying and categorizing DRP in peroral drug administration considering their clinical risk and preventability by UDSS/CPOE/CDSS. Investigations: In surgical and internal-medicine departments, we observed routine procedures in peroral drug administration for DRP. An expert panel including pharmaceutical and nursing expertise categorized the identified 18 DRP categories into three levels: DRP that have not yet resulted in medication errors (ME) (Level-I), DRP where ME have occurred but have not yet reached the patient (Level-II), and DRP where ME have occurred and have reached the patient (Level-III). Additionally, the panel categorized DRP according to their clinical risk and whether the implementation of UDSS/CPOE/CDSS can prevent them. Results: In 77 surgical patients, 1,849 peroral drug administration procedures, and in 149 internal-medicine patients, 1,405 procedures were observed. The 18 DRP categories were identified with a frequency of 0.6%-26.7% (Level-I), 0.1%-21.5% (Level-II), and 0.0%-1.0% (Level-III). Of those, four categories were considered of high clinical risk: "Name of the medication is not readable", "Prescribed medication is not prepared for administration", "An incorrect or non-prescribed medication is prepared", and "A medication is prepared for the wrong patient (mix-up)". Twelve DRP categories were categorized as highly preventable by UDSS/CPOE/CDSS. Conclusions:Under routine conditions, we identified a substantial number of DRPs. An expert panel categorized many of those DRPs as clinically highly relevant and highly preventable by UDSS/CPOE/CDSS.

Physiologic changes due to aging, pregnancy, nutritional status, drug interactions, and can affect pharmacokinetics and pharmacodynamics of antiepileptic drugs. In this review article, the interactions between phenytoin and herbs recorded in the literature were summarized according to the Medline database (via PubMed). Our results revealed that, changes in phenytoin's bioavailability were reported for co-administration of herbs or herbal extracts. An increase in phenytoin blood levels was established with Piper nigrum, Mentat, and Lipidum sativum in in vitro and/or in vivo studies. In contrast, herbphenytoin interactions led to sub-therapeutic levels of phenytoin in other cases with herbs such as Cannabis, Ginkgo biloba, Morinda citrifolia, Nigella sativa, and Trigonella foenum graceum. In addition, the findings of other pharmcodynamic experiments showed that various herbs, including Zizyphus jujube, Terminalia chebula, Curcuma longa L, and Centella asiatica, improved the pharmacological impact of phenytoin. To reduce the patients' health risks, health professionals involved in their treatment are expected to be thoroughly educated about the interactions between phenytoin and medicinal plants.

The focus of this study was to examine whether the conversion of cytotoxic conjugated unsaturated ketones (or enones) into the corresponding thiol adducts leads to a reduction or abolition of cytotoxic potencies. A number of enones and related thiol adducts were evaluated against human HCT116 and HT29 colon cancer cells. Some 63% of the IC₅₀ values are less than 10 μM and several compounds are more toxic than 5-FU. The thiol adducts are either more potent or are equipotent with the corresponding enones. A number of compounds are far more toxic to HCT116 and HT29 neoplasms than non-malignant CRL1790 cells leading to impressive Selectivity Index figures. An additional positive feature of these compounds is that they have favorable ADME properties.

Hovenia dulcis has been reported to have various pharmacological activities, but most studies were done with its fruits. However, from an economic point of view, the use of discarded leaves and branches as by-products is very valuable. In this study, thein vitro andin vivo anti-obesity activities of Hovenia dulcis branch extract (HDB) were investigated to evaluate the applicability of HDB as an anti-obesity agent. In differentiated 3T3-L1 cells, HDB inhibited lipid droplet accumulation. And HDB downregulated CEBPα, PPARγ, and perilipin-1, and upregulated ATGL, p-HSL, HSL, p-AMPK, UCP-1, PGC-1α, PRDM16, LC3-II, and p62/SQSTM1. In addition, HDB increased free glycerol content. In HFD-induced obese mice, HDB reduced body weight and total fat weight. In addition, HDB decreased blood LDL-cholesterol, blood total cholesterol, and blood triglyceride. These results indicate that HDB has anti-obesity activity and HDB can be used as a healthy functional food agent for weight reduction.

Cardiac rehabilitation in patients with diabetes mellitus and heart failure may be affected by anti-diabetic drugs. However, there are few reports on the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiac rehabilitation. Thus, we retrospectively investigated the patient backgrounds and effects of cardiac rehabilitation in 44 patients admitted to our hospital with heart failure and pre-existing diabetes mellitus. Our results showed that the patients tended to be older, and those who received SGLT2 inhibitors had lower systolic blood pressure and left ventricular ejection fraction on admission than those who did not. Cardiac rehabilitation significantly improved the Short Physical Performance Battery (SPPB) score in all patients, and there was no significant difference in body mass index or in body weight. There were no significant differences in SPPB score at admission, discharge, or change from admission to discharge with or without SGLT2 inhibitors. These results suggest that SGLT2 inhibitors do not affect the change in SPPB scores. SGLT2 inhibitors may thus be used safely without affecting cardiac rehabilitation while adhering to the necessary safety precautions.

In powder formulations, it is a problem that the required therapeutic dose is not obtained because of loss of the active pharmaceutical ingredient (API). In this study, we investigated three types of lactose diluents, which are widely used as pharmaceutical excipients, for dispensing prednisolone powder. Extra-fine crystalline lactose, commonly used as a diluent in compounding powder formulations, was used as a comparison. The effect of lactose on the API loss rate was examined by analyzing the amount of prednisolone in the powder formulation taken out of a single-dose package after dispensing. The results showed that Dilactose-F had the lowest API loss rate (22%), followed by powder lactose (37.8%), extra-fine crystalline lactose (45.9%), and crystal form lactose (48.6%), indicating that the use of Dilactose-F as a diluent significantly improved API loss when compounding the powder formulation. Because each mixture of commercial prednisolone powder and lactose was within acceptable uniformity and loss rate before packaging, we considered that API loss occurred when the powder was taken out of the single-dose package before patients ingested them. Then, the physical properties of these lactose types affecting the API loss rate were examined. Strong correlation was not found between flowability and the API loss rate, but particle size distribution and bulk density were strongly correlated with the API loss rate. Furthermore, Dilactose-F, which showed the lowest API loss rate, did not show an exothermic peak due to epimerization to anhydrous β -lactose in differential scanning calorimetry and showed a peak specific to β -lactose in powder X-ray diffractometer. These results suggested that in powder compounding where the API content is low, the physical properties of lactose, such as particle size distribution, bulk density, and crystalline form, are intricately related to API loss.

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Glioblastoma is a highly malignant and invasive brain tumor, and there is an urgent need to establish a treatment option that prevents its growth and metastasis. Blonanserin is an antipsychotic drug widely used in the treatment of schizophrenia. It has recently been reported to inhibit the growth of breast cancer cells. In this study, we investigated the effect of blonanserin on the proliferation and migration of glioblastoma cells. The anti-proliferative activity of blonanserin was evaluated in terms of cell viability, competition, and cell death pathways in glioblastoma. Cell viability studies showed that blonanserin had growth inhibitory ability regardless of the malignancy of glioblastoma cells, but at concentrations close to its IC₅₀, it only had a slight cell death-inducing effect. Blonanserin showed growth inhibitory activity without D₂ antagonism following an independent competition analysis using blonanserin and D₂ antagonists. When the anti-migration activity of U251 cells was measured, blonanserin was found to attenuate cell migration. Furthermore, treatment with blonanserin at concentrations close to its IC₅₀ value inhibited extensive filament actin formation. In conclusion, blonanserin inhibited the proliferation and migration of glioblastoma cells independent of D₂ antagonism. The present study shows that blonanserin may serve as a seed compound for the discovery of new glioblastoma therapeutics to prevent the growth and metastasis of glioblastoma.