著者

Yuichi Muraki Ryuji Koizumi Yoshiki Kusama Ryo Inose Masahiro Ishikane Norio Ohmagari

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1490-1493, 2023-10-01 (Released:2023-10-01)

参考文献数

14

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Voriconazole (VRCZ) is an antifungal drug that necessitates therapeutic monitoring (TDM). Typically, TDM is recommended for patients undergoing long-term outpatient treatment. However, in Japan, insurance reimbursement for TDM is only permitted for inpatients. There is a concern that VRCZ use is growing among outpatients, although information regarding this issue remains unavailable. Therefore, we aimed to clarify the use of VRCZ by utilizing data from the National Database of Health Insurance Claims and Specific Health Checkups in Japan. The use of branded and generic oral VRCZ from 2013 to 2019 was calculated using the defined daily doses/1000 inhabitants/d (DID) for each receipt type. Oral VRCZ was used more frequently in the outpatient setting than that in the inpatient setting, with use increasing over time. The use of generic drugs began in 2016 and accounted for 52.5% of the use in 2019 among outpatients. Considering outpatient prescriptions, 76.4–81.0% were dispensed at insurance pharmacies, indicating the need for community pharmacist involvement. Accordingly, the appropriate use of VRCZ in ambulatory care should be promoted in collaboration with community pharmacists, and a reimbursement system should be established to implement TDM in ambulatory care.

著者

Eiichi Goto Tatsuaki Tagami Koki Ogawa Tetsuya Ozeki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1461-1467, 2023-10-01 (Released:2023-10-01)

参考文献数

34

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Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated. The azithromycin-loaded contact lenses were composed of the cross-linking reagent polyethylene glycol diacrylate (PEGDA), PEG 400 as a solvent, a photoinitiator, and azithromycin. The 3D-printed contact lenses were fabricated successfully, and formulations with lower PEGDA concentrations produced thicker lenses. The mechanical strength of the PEGDA-based contact lenses was dependent on the amount of PEGDA and was improved by a second curing process. Drug release from 3D-printed contact lenses was reduced in the samples with a second curing process. The azithromycin-loaded contact lenses exhibited antimicrobial effects in vitro for both Gram-positive and -negative bacteria. These results suggest that 3D-printed contact lenses containing antibiotics are an effective model for treating eye infections by controlling drug release.

著者

Mariko Kawana Akime Miyasato Miyui Funato Keigo Nagatani Norifumi Suzuki Chiharu Onoda Hidenori Fujimoto Rintaro Ohno Ayuko Kusakabe Mio Kiribayashi Kazuyo Nakamura Masayoshi Kondo Ayumi Ozeki Kousuke Okamoto Hideya Kokubun

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1444-1450, 2023-10-01 (Released:2023-10-01)

参考文献数

13

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In Japan, a low-dose transdermal fentanyl (TDF; 0.5 mg) has been approved to address pain in opioid-naïve patients with cancer; however, efficacy and safety data are lacking. To determine the efficacy and safety of TDF, patients with opioid-naïve cancer pain prescribed TDF (0.5 mg/d) and oral oxycodone sustained-release formulation (OXY) 10 mg/d were extracted from electronic medical and nursing records. Overall, 40 and 101 subjects were analyzed in the TDF and OXY groups, respectively. Compared with baseline (median [minimum, maximum]) values, changes in the Numerical Rating Scale (NRS) score on days 1, 3, and 7 post-administration were as follows: TDF (0 [−5, 4]) and OXY (−1.0 [−8, 3]); TDF (−1.5 [−6, 3]) and OXY (−2.0 [−8, 4]); and TDF (−2.0[−6, 3]) and OXY (−3.0[−8, 5]), respectively. No significant difference was observed between the groups on days 1 and 3; however, the change in the NRS on day 7 was significantly higher in the OXY group than that in the TDF group. Regarding adverse events, nausea occurred in 12.5 and 13.9% of patients in the TDF and OXY groups, respectively, while 12.5% of TDF- and 10.9% of OXY-treated patients experienced somnolence, revealing similar occurrence in both groups. However, constipation was more common in the OXY group (TDF: 50.0%, OXY: 71.3%). No serious adverse events (e.g., respiratory depression) were observed in either group. Low-dose TDF (0.5 mg), available only in Japan, showed comparable efficacy and safety to OXY (10 mg/d) and can be a first choice for opioid-naïve patients with cancer pain.

著者

Shohei Nakamura Nanami Ito Ayumi Sakurada Takatoshi Sakamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.9, pp.687-694, 2023-09-01 (Released:2023-09-01)

参考文献数

43

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Lactose is an excipient used extensively for bulking, diluting, and molding active pharmaceutical ingredients in tablet manufacturing. Particularly, granulated lactose (GL) intended for direct powder compression has distinct properties due to differences in manufacturing methods. It contributes to handling blended powders for tableting and tablet quality. In this study, we aimed to compare the functions of different forms of GL added as excipients during direct powder compression on the tablet properties and the effect of magnesium stearate (Mg-S) used as a lubricant on each type of GL. Different GL types obtained using different manufacturing methods (agitated granulation, GL-AG; spray-dried granulation, GL-SD; fluidized bed granulation, GL-FB) were blended with maize starch, low-substituted hydroxypropyl cellulose, and paracetamol in a V-type blender for 10 min. Mg-S was added at varying amounts (0.1, 1.0, and 2.0%) and blending times (5, 10, and 30 min) for the nine types of blended powders for tableting formulation. The powders were tableted, and the tablets were evaluated for weight and drug loading variations, tensile strength, friability, and disintegration time. When tablets with the same blending conditions were compared, the tensile strength and disintegration time were in the order of GL-FB > GL-SD > GL-AG. For each GL, we analyzed the effects of changes in the added amount of Mg-S and blending time using contour plots, evaluated the effects of blending conditions on tablet properties, and determined the target tablet properties. We investigated the optimization of the lubricant blending conditions to obtain suitable tablets.

著者

Tomoaki Ishida Kei Kawada Kohei Jobu Tetsushi Kawazoe Naohisa Tamura Mitsuhiko Miyamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.4, pp.460-466, 2022-04-01 (Released:2022-04-01)

参考文献数

34

被引用文献数

2

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Bofutsushosan is a traditional Japanese Kampo medicine. In recent years, it has been reported to be effective in the treatment of lifestyle-related diseases, and its use is increasing. However, side effects from bofutsushosan administration are common, with drug-induced liver injury being the most frequently reported complication. In this study, we analyzed the Japanese Adverse Drug Event Report (JADER) database regarding the occurrence of liver injury after bofutsushosan administration. The results showed that bofutsushosan presented a significant reporting odds ratio (ROR) signal [crude ROR 14, 95% confidence interval (CI) 12–17; p < 0.001], indicating liver injury. Furthermore, the incidents of adverse events following bofutsushosan administration, as recorded in the JADER database, were higher in women aged between 30 and 59 years. The results of logistic regression analysis in patients taking this agent showed that females in the aforementioned age range had higher odds of developing drug-induced liver injury (adjusted ROR 5.5, 95% CI 2.8–11; p < 0.001). Therefore, although bofutsushosan is a useful drug for lifestyle-related diseases, it may be necessary to refrain from its overuse, and caution should be taken during its occasional use to avoid severe adverse events.

著者

Renfeng Qiu Shuxiao Chen Fang Hua Shuai Bian Jianfeng Chen Gang Li Xuejun Wu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.9, pp.1254-1262, 2021-09-01 (Released:2021-09-01)

参考文献数

60

被引用文献数

8

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Betanin, a bioactive ingredient mostly isolated from beetroots, exhibits a protective effect against cardiovascular diseases. However, its effects on abdominal aortic aneurysm (AAA) have not been elucidated. In this study, an AAA model was constructed by infusion of porcine pancreatic elastase in C57BL/6 mice. Mice were then administered with betanin or saline intragastrically once daily for 14 d. Our results showed that treatment with betanin remarkably limited AAA enlargement and mitigated the infiltration of inflammatory cells in the adventitia. The increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) was also significantly alleviated following betanin treatment. Furthermore, betanin suppressed the activation of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling in the aortic wall, and downregulated the levels of tissue-reactive oxygen species as well as circulating 8-isoprostane by stimulating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Taken together, these data suggest that betanin may attenuate AAA progression and may be used as a therapeutic drug against AAA.

著者

Shota Kawai Shunsuke Takashima Masafumi Ando Sayaka Shintaku Shigemitsu Takeda Kazuya Otake Yuma Ito Masaki Fukui Megumi Yamamoto Yoshimichi Shoji Hiroaki Shirahase Tatsuya Kitao

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.9, pp.701-716, 2023-09-01 (Released:2023-09-01)

参考文献数

27

被引用文献数

1

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The readthrough mechanism, which skips the premature termination codon and restores the biosynthesis of the defective enzyme, is an emerging therapeutic tactic for nonsense mutation-related diseases, such as Hurler syndrome, a type of mucopolysaccharidosis. In the present study, novel triaryl derivatives were synthesized and their readthrough-inducing activities were evaluated by a luciferase reporter assay with a partial α-L-iduronidase (IDUA) DNA sequence containing the Q70X nonsense mutation found in Hurler syndrome and by measuring the enzyme activity of IDUA knockout cells transfected with the mutant IDUA gene. KY-516, a representative compound in which the meta position carboxyl group of the left ring of the clinically used ataluren was converted to the para position sulfamoylamino group, the central ring to triazole, and the right ring to cyanobenzene, exhibited the most potent readthrough-inducing activity in the Q70X/luciferase reporter assay. In Q70X mutant IDUA transgenic cells, KY-516 significantly increased enzyme activity at 0.1 µM. After the oral administration of KY-516 (10 mg/kg), the highest plasma concentration of KY-516 was above 5 µM in rats. These results indicate that KY-516, a novel triaryl derivative, exhibits potent readthrough-inducing activity and has potential as a therapeutic agent for Hurler syndrome.

著者

Norihisa Noguchi Hidemasa Nakaminami Keisuke Nakase Masanori Sasatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.9, pp.1469-1473, 2011-09-01 (Released:2011-09-01)

参考文献数

25

被引用文献数

16 19

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Probiotics are additives containing live microbes that beneficially affect a host by improving the properties of the host intestinal microflora. Recently, advances in medical treatments have led to increased numbers of immunocompromised patients; some patients contract opportunistic infections of Enterococcus species, which are considered non-pathogenic bacteria. To evaluate the safety of probiotics containing Enterococcus strains, we isolated Enterococcus from six probiotic products and compared the pathogenic genes and antimicrobial susceptibility of the probiotic strains to those of clinical isolates. Our study showed that all Enterococcus strains contained in probiotic products were E. faecium, and no vancomycin-resistant strains were found. In addition, no pathogenic genes, such as ace, agg, gelE, cylM, cylB, cylA, cpd, cob, ccf, efaAfs, efaAfm, espfs, or espfm, were found in the probiotic strains. Pulsed-field gel electrophoresis (PFGE) analysis showed obvious genetic differences between the probiotic strains and the clinical isolates. The data suggested that the probiotic Enterococcus strains were not transmitted to hospitalized patients. Therefore, our results strongly suggest that probiotic products are unlikely agents for causing opportunistic infections.

著者

Rie Ito Chisa Takemura Hiroshi Akiyama Koichi Saito

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.4, pp.312-317, 2023-04-01 (Released:2023-04-01)

参考文献数

15

被引用文献数

1

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The degradation behavior of three benzodiazepines (BZPs)—lormetazepam (LMZ), lorazepam, and oxazepam—with hydroxy groups on the diazepine ring in artificial gastric juice and the effect of storage pH conditions on drug degradability were monitored using an LC/photodiode array detector (PDA) to estimate their pharmacokinetics in the stomach. Although the three BZPs degraded in artificial gastric juice, none could be restored, despite increasing the storage pH, implying that the degradation reaction was irreversible. As for LMZ, we discussed the physicochemical parameters, such as the activation energy and activation entropy involved in the degradation reaction as well as the reaction kinetics; one of the degradation products was isolated and purified for structural analysis. In the LMZ degradation experiment, peaks corresponding to degradation products, (A) and (B), were detected through the LC/PDA measurements. Regarding the degradation behavior, we hypothesized that LMZ was degraded into (B) via (A), where (A) was an intermediate and (B) was the final product. Although the isolation of degradation product (A) was challenging, degradation product (B) could be isolated and was confirmed to be “methanone, [5-chloro-2-(methylamino)phenyl](2-chlorophenyl)-” based on structure determination using various instrumental analyses. The compound exhibited axis asymmetry as determined using single-crystal X-ray structure analysis. Because the formation of degradation product (B) was irreversible, it would be prudent to target the final degradation product (B) and LMZ for identification when detecting LMZ in human stomach contents, such as during forensic dissection.

著者

Yo Shinoda Masahiro Akiyama Takashi Toyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.9, pp.1162-1168, 2023-09-01 (Released:2023-09-01)

参考文献数

109

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Methylmercury (MeHg) is the causal substrate of Minamata disease and a major environmental toxicant. MeHg is widely distributed, mainly in the ocean, meaning its bioaccumulation in seafood is a considerable problem for human health. MeHg has been intensively investigated and is known to induce inflammatory responses and neurodegeneration. However, the relationship between MeHg-induced inflammatory responses and neurodegeneration is not understood. In the present review, we first describe recent findings showing an association between inflammatory responses and certain MeHg-unrelated neurological diseases caused by neurodegeneration. In addition, cell-specific MeHg-induced inflammatory responses are summarized for the central nervous system including those of microglia, astrocytes, and neurons. We also describe MeHg-induced inflammatory responses in peripheral cells and tissue, such as macrophages and blood. These findings provide a concept of the relationship between MeHg-induced inflammatory responses and neurodegeneration, as well as direction for future research of MeHg-induced neurotoxicity.

著者

Kunio Kosaka Toshio Yokoi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.11, pp.1620-1622, 2003 (Released:2003-11-01)

参考文献数

13

被引用文献数

49 57

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Nerve growth factor (NGF) is a factor vital for the growth and functional maintenance of nerve tissue. The authors found that a rosemary (Rosmarinus officinalis L.) extract enhanced the production of NGF in T98G human glioblastoma cells. Furthermore, the results indicated that carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF.

著者

Takashi Kitahara Nao Koyama Junichi Matsuda Yuko Aoyama Yoichi Hirakata Shimeru Kamihira Shigeru Kohno Mikiro Nakashima Hitoshi Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.27, no.9, pp.1321-1326, 2004 (Released:2004-09-01)

参考文献数

36

被引用文献数

78 92

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The objective of this study was to investigate the antimicrobial activities of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of saturated fatty acids and fatty amines was determined by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the saturated fatty acids, showed antimicrobial activity at 400 μg/ml against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concentration (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 μg/ml; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, respectively. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 saturated fatty acids and 3 fatty amines was examined in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of saturated fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, especially in the case of insoluble substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.

著者

Yasuyuki Sadzuka Chieko Inoue Saho Hirooka Tomomi Sugiyama Keizo Umegaki Takashi Sonobe

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.28, no.9, pp.1702-1706, 2005 (Released:2005-09-01)

参考文献数

42

被引用文献数

19 19

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We previously showed that theanine, is a major amino acid in green tea, enhanced doxorubicin (DOX) induced antitumor activity. Besides, theanine induced the elevation of glutathione (GSH) level attributable to the increase of glutamate in the liver of mice, namely theanine would reduce the adverse reaction of DOX. Consequently, theanine was thought to be effective against the tissue changes with GSH level reduction. On the other hand, it is suggested excessive uptake of alcohol causes a production of free radicals, a decrease of GSH level, and an increase in the amount of lipid peroxide (LPO) in liver, and shifting to an alcoholic liver injury. Then, aiming at the prevention and medical treatment of a hepatic toxicity by the food components with little toxicity, we have studied the effect of theanine (i.p.) on ethanol metabolism and hepatic toxicity using ethanol (p.o.) single-administered mice. On the 1st hour after ethanol administration, the ethanol concentrations in blood of the theanine combined groups decreased compared with the ethanol-alone group. The alcohol dehydrogenase and aldehyde dehydrogenase activities in the liver increased by combined theanine. Since the elevation of cytochrome P450 (CYP) 2E1 activity was controlled in the theanine-combined groups, it was considered that these disorders attributable to CYP2E1 in ethanol long-term uptake might be avoidable by theanine. Although LPO increased in 3 h after by single-administration of ethanol, the increase was controlled by theanine-administration and was improved until the normal level. In conclusion, it was indicated that theanine was effective against alcoholic liver injury.

著者

Tadashi Fujita Atsushi Kawase Toshiro Niwa Norimichi Tomohiro Megumi Masuda Hideaki Matsuda Masahiro Iwaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.5, pp.925-930, 2008-05-01 (Released:2008-05-01)

参考文献数

45

被引用文献数

36 40

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In a previous study we found that 50% ethanol extracts of immature fruits of Citrus unshiu (satsuma mandarin) have anti-allergic effects against the Type I, II and IV allergic reactions. However, many adverse interactions between citrus fruit, especially grapefruit juice, and drugs have been reported due to the inhibition of cytochrome P450 (CYP) activities. The purpose of this study was to examine the competitive inhibitory effects of extracts from immature citrus fruit on CYP activity. Extracts were prepared from 12 citrus species or cultivars, and were tested against three kinds of major CYPs, CYP2C9, CYP2D6 and CYP3A4, in human liver microsomes. We also estimated the amounts of flavonoids (narirutin, hesperidin, naringin and neohesperidin) and furanocoumarins (bergapten, 6′,7′-dihydroxybergamottin and bergamottin) in each extract using HPLC. Citrus paradisi (grapefruit) showed the greatest inhibition of CYP activities, while Citrus unshiu which has an antiallergic effect, showed relatively weak inhibitory effects. Extracts having relatively strong inhibitory effects for CYP3A4 tended to contain higher amounts of naringin, bergamottin and 6′,7′-dihydroxybergamottin. These results, providing comparative information on the inhibitory effects of citrus extracts on CYP isoforms, suggest that citrus extracts containing high levels of narirutin and hesperidin and lower levels of furanocoumarins such as C. unshiu are favorable as antiallergic functional ingredients.

著者

Tadashi Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.3, pp.364-378, 2023-03-01 (Released:2023-03-01)

参考文献数

187

被引用文献数

7

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The interleukin 6 (IL-6) family of cytokines is defined by the usage of gp130, a common β-receptor signaling subunit, which promotes a variety of signals. They induce many biological functions on many cell types, including immune and inflammatory cells. They also exhibit hormone-like features, which are involved in homeostatic processes. Signal transducer and activator of transcription 3 (STAT3) is a significant signaling molecule fundamental in regulating IL-6/gp130 and is highly implicated in pathological conditions; therefore, STAT3 activation is tightly regulated through various mechanisms and at multiple levels. There is a large amount of information about STAT3-interacting proteins, which positively or negatively regulate STAT3 activity. This review is focused on IL-6-mediated signal transduction and the introduction of novel STAT3-binding partners. The review will help develop new strategies for clinically controlling the functions of IL-6/STAT3.

著者

Masaki Hirabatake Hiroaki Ikesue Shintaro Yoshino Mayu Morimoto Toshinari Yamasaki Tohru Hashida Mutsushi Kawakita Nobuyuki Muroi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.8, pp.1065-1071, 2023-08-01 (Released:2023-08-01)

参考文献数

25

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Pazopanib is one of recommended treatment for metastatic renal cell carcinoma (RCC). Despite its effectiveness, patients often difficult to continue pazopanib treatment due to adverse events (AEs). We established an ambulatory care pharmacy practice that enables pharmacist–urologist collaboration to manage patients with RCC. This study evaluated the usefulness of this collaborative management. We retrospectively reviewed the medical records of 51 consecutive patients with metastatic RCC receiving pazopanib at the Kobe City Medical Center General Hospital between April 2014 and December 2020. Our collaborative management was implemented in October 2016. The time to pazopanib discontinuation was compared between patients who started pazopanib before (n = 30) and after (n = 21) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with pazopanib discontinuation. In the collaborative management, the oncology pharmacists had a total of 245 face-to-face patient consultations, and provided 286 suggestions [according to supportive care in pazopanib treatment (214 suggestions) were most frequent], and 236 (82.5%) were accepted by urologists. The median time to discontinuation (6.1 months vs. 2.4 months, p = 0.024) was significantly longer in the after group. Multivariate analysis showed that collaborative management (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.26–0.88, p = 0.017), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at pazopanib initiation (HR 3.87, 95% CI 1.47–9.13, p = 0.008) were significantly associated with pazopanib discontinuation. These results suggested that, compared to conventional management, collaborative management is effective at prolonging the time to pazopanib discontinuation.

著者

Shota Tokunaga Chie Uchikoshi Kyu Hayashi Hironori Suzuki Masataka Ito Shuji Noguchi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.8, pp.633-640, 2023-08-01 (Released:2023-08-01)

参考文献数

45

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Nobiletin (NOB) is a flavonoid with attractive pharmaceutical characteristics, including anti-Alzheimer’s, anti-inflammation, and anti-cancer properties, but it has low solubility in water, resulting in reduced bioavailability. Its solubility must be improved to develop NOB as a drug. Cocrystal engineering can change the physicochemical properties of an active pharmaceutical ingredient and generate remarkable drug candidates that are superior in drug formulation. In this report, extensive co-crystal screening of NOBs with 31 cocrystal formers (coformers) with various functional groups was carried out by the liquid-assisted grinding method. As a result, four cocrystals (NOB with urea (URE), oxalic acid, gallic acid and salicylic acid) and one solvate crystal (NOB with formic acid (FOR)) were found. Powder X-ray diffraction and thermal analysis revealed the unique crystal morphology of all the obtained samples. In addition, the crystal structures of two of them (NOB-URE and NOB-FOR) were determined by single crystal X-ray diffraction. The results revealed that NOB-URE and NOB-FOR are new cocrystals or solvate crystals consisting of molar ratios of 1 : 2 and 1 : 0.73, respectively. In NOB-URE, we could observe a transient increase in solubility due to supersaturation, suggesting that URE is one of the better coformers of NOB.

著者

Kota Sakuraba Yukio Kojima Takaaki Terahara Hidekazu Kuma Yoshihiro Tokudome

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b23-00294, (Released:2023-07-31)

参考文献数

24

被引用文献数

1

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Recently, microneedling as a cosmetic product has attracted attention as one way to improve skin barrier function and moisturizing function to reduce wrinkle formation. However, some cases of erythema and edema have been reported as side effects. In order to develop safer microneedle cosmetics, we investigated whether microneedles can improve skin barrier function and moisturizing function even when applied in a non-invasive manner that does not penetrate the stratum corneum. We established the condition of non-penetrating microneedle application on reconstructed human full-thickness skin models and examined the effect on the skin models when microneedles were applied under this condition. Microneedle application increased the gene expression of serine palmitoyltransferase long chain base subunit (SPTLC) 3, filaggrin, and transglutaminase 1. The amount of ceramide produced by SPTLC was also increased by microneedle application. Gene expression of filaggrin-degrading enzymes and the amount of free amino acids, a product of filaggrin degradation, were also increased by microneedling. These results suggest that non-invasive microneedle application can improve skin barrier function and moisturizing function by increasing the amount of ceramide and natural moisturizing factors.

著者

Kenshi Takechi Yurika Yoshioka Hitoshi Kawazoe Mamoru Tanaka Shingo Takatori Miwako Kobayashi Ichiro Matsuoka Hiroaki Yanagawa Yoshito Zamami Masaki Imanishi Keisuke Ishizawa Akihiro Tanaka Hiroaki Araki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.10, pp.1775-1778, 2017-10-01 (Released:2017-10-01)

参考文献数

17

被引用文献数

7 8

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Treatment with antipsychotic drugs has been associated with hyperprolactinemia. The same antipsychotic drugs have also been associated with side effects such as menstruation disorders. The aim of this study was to evaluate the prevalence of hyperprolactinemia and menstruation disorders in women undergoing antipsychotic treatment. We performed a retrospective chart review study of psychiatric patients who underwent laboratory testing for serum prolactin (PRL) level between March 2011 and March 2015 in Ehime University Hospital. Patients presenting with and without menstruation disorders were evaluated to determine if they presented concomitant hyperprolactinemia. Patients with menstrual disorders had a significant increase in serum PRL level with a mean of approximately 90 ng/mL. Those with menstrual disorders presented increased PRL levels by 2-fold that of patients without menstrual disorder. However, there was no significant difference in the equivalent dose of chlorpromazine between these two groups. Additionally, about 70% of patients with menstrual disorders received risperidone treatment. The receiver operating characteristic curve showed that the optimal cutoff point of serum PRL level associated with the development of menstrual disorders was 60 ng/mL. Based on these results, we concluded that patients with menstrual disorders presented increased serum PRL, and that most of them underwent treatment with risperidone.

著者

Takehiro Yamada Shungo Imai Yasuyuki Koshizuka Yuki Tazawa Keisuke Kagami Naoki Tomiyama Ryosuke Sugawara Akira Yamagami Tsuyoshi Shimamura Ken Iseki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.7, pp.1112-1118, 2018-07-01 (Released:2018-07-01)

参考文献数

31

被引用文献数

15 17

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Therapeutic drug monitoring for voriconazole, an antifungal agent, is essential for maximizing efficacy and preventing toxicity. The aim of this study was to elucidate the optimal maintenance dose of voriconazole in patients with severe liver cirrhosis (Child–Pugh class C) by reviewing the plasma trough concentrations obtained by therapeutic drug monitoring and daily doses of voriconazole. We retrospectively evaluated 6 patients with Child–Pugh class C cirrhosis who received oral voriconazole treatment and were liver transplant recipients or were awaiting liver transplantation. We compared their voriconazole trough concentrations and daily maintenance doses to those of patients who did not have liver cirrhosis (n=56). We found that plasma voriconazole trough concentrations in all patients with Child–Pugh class C were almost within therapeutic range, and the median plasma trough concentration at steady state was not significantly different from that of patients who did not have liver cirrhosis. In addition, the median daily maintenance dose of voriconazole was significantly lower (2.13 mg/kg/d) than that of the control patients (6.27 mg/kg/d), suggesting that trough voriconazole concentrations are elevated in Child–Pugh class C patients. Thus, we conclude that oral voriconazole maintenance doses in patients with Child–Pugh class C should be reduced to approximately one-third that of patients with normal liver function, with the follow-up dose adjusted by therapeutic drug monitoring.