著者

Sho Masui Atsushi Yonezawa Kenji Momo Shunsaku Nakagawa Kotaro Itohara Satoshi Imai Takayuki Nakagawa Kazuo Matsubara

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.3, pp.323-332, 2022-03-01 (Released:2022-03-01)

参考文献数

55

被引用文献数

6

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Infliximab (IFX) has contributed to the treatment of several chronic inflammatory diseases, including Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (Pso), and rheumatoid arthritis (RA). However, the loss of response in some patients with long-term IFX therapy has been a major problem. Randomized controlled trials (RCTs) are limited in their short duration and lack of generalizability to the real-world population. We aimed to describe the persistence rates of IFX therapy to estimate its long-term effectiveness in clinical practice. Claims data from the Japan Medical Data Center database from January 2005 to June 2017 were used. The study population was identified based on the International Classification of Diseases, 10th Revision and the Anatomical Therapeutic Chemical Classification System. The 5-year persistence rates of IFX therapy were estimated using the Kaplan–Meier method. Overall, 281, 235, 41, and 222 patients with CD, UC, Pso, and RA, respectively, were selected. The 5-year persistence rates for IFX claims were 62.9, 38.9, 22.1, and 28.1% in patients with CD, UC, Pso, and RA, respectively. Patients with CD and UC administered IFX beyond the median dose had higher persistence rates. In patients with RA, female sex and no prior use of other biologics were associated with longer persistence. In conclusion, IFX persistence rates differed across chronic inflammatory diseases, which did not correspond to the results of the major RCTs. Factors associated with longer IFX persistence were identified in each disease group. Our findings may provide useful information to facilitate the proper use of IFX.

著者

Takahiko Fujikawa Nariyasu Kanada Akihide Shimada Masato Ogata Ikukatsu Suzuki Ikuo Hayashi Kunio Nakashima

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.1, pp.169-172, 2005 (Released:2005-01-01)

参考文献数

15

被引用文献数

31 38

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The aim of this study was to determine whether sesamin, a component from Acanthopanax senticosus HARMS (ASH) pharmacologically offers protection against Parkinson's disease (PD) and its related depressive behavior in rats administered rotenone. We also examined how sesamin affected the rotenone-induced loss of tyrosine hydroxylase (TH) or glial cell line-derived neurotrophic factor (GDNF)-positive neurons in the midbrain of rats. Rats were orally administered sesamin (3, 30 mg/kg) once a day for 2 weeks before an intraperitoneal injection of rotenone (2.5 mg/kg). The pole test and catalepsy test were used to evaluate the effects of sesamin administration on bradykinesia and depressive behaviors in the PD model of rats given rotenone for 5 weeks. Those effects were compared with the ASH administrated group (250 mg/kg). Treatment with sesamin for seven weeks resulted in prophylactic effects on rotenone-induced parkinsonian bradykinesia and catalepsy, and the effects were equivalent to ASH effects. Immunohistochemistical analysis using TH or GDNF antibody showed that sesamin provided cytoprotective effects against rotenone-induced loss of DA cells. The results suggest that it may be possible to use the ASH and sesamin for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to pesticide or environmental neurotoxins in general.

著者

Fumihiro Nishimura Tomoko Ushijima Masako Nojima Shinsuke Hamada Kazumasa Hara Yasuyuki Hamada Daisuke Kadowaki Shigeyuki Miyamura Kentaro Oniki Junji Saruwatari

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.10, pp.1427-1432, 2021-10-01 (Released:2021-10-01)

参考文献数

27

被引用文献数

3

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Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

著者

Takanori Miyoshi Hiroo Miyashita Naomi Matsuo Miki Odawara Minako Hori Yoichi Hiraki Hirofumi Kawanaka

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.10, pp.1413-1418, 2021-10-01 (Released:2021-10-01)

参考文献数

20

被引用文献数

1

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The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1–3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0–24 h), delayed phase (24–120 h), and overall phase (0–120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

著者

Shinsuke Yamashita Shungo Imai Kenji Momo Hitoshi Kashiwagi Yuki Sato Mitsuru Sugawara Yoh Takekuma

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.8, pp.1151-1155, 2021-08-01 (Released:2021-08-01)

参考文献数

30

被引用文献数

1

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Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.

著者

Makoto Tsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.12, pp.1959-1968, 2019-12-01 (Released:2019-12-01)

参考文献数

132

被引用文献数

15 49

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Pain is a defense system that responds rapidly to harmful internal and external stimuli through the somatosensory neuronal pathway. However, damage to the nervous system through cancer, diabetes, infection, autoimmune disease, chemotherapy or trauma often leads to neuropathic pain, a debilitating chronic pain condition. Neuropathic pain is not simply a temporal continuum of acute nociceptive signals from the periphery, but rather due to pathologically altered functions in the nervous system, which shift the net neuronal excitatory balance toward excitation. Although alterations were long thought to be a result of changes in neurons, but an increasing body of evidence over the past decades indicates the necessity and sufficiency of microglia, the tissue-resident macrophages of the spinal cord and brain, for nerve injury-induced malfunction of the nervous system. In this review article, I describe our current understanding of the molecular and cellular mechanisms underlying the role of microglia in the pathogenesis of neuropathic pain and discuss the therapeutic potential of microglia from recent advances in the development of new drugs targeting microglia.

著者

Tomoaki Ishida Kei Kawada Shumpei Morisawa Kohei Jobu Yasuyo Morita 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.43, no.10, pp.1570-1576, 2020-10-01 (Released:2020-10-01)

参考文献数

24

被引用文献数

1 18

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Yokukansan is a Kampo formula that is commonly used by the elderly because it is expected to improve peripheral symptoms of dementia and delirium. However, side effects from its use are frequently reported in the elderly. In particular, pseudoaldosteronism caused by the licorice contained in yokukansan leads to hypertension, hypokalemia, and muscle weakness, which may result in death. This study aimed to identify the risk factors of pseudoaldosteronism with yokukansan use. Using cases reported in the Japanese Adverse Drug Report (JADER) database, the reporting odds ratio (ROR) was calculated and compared to assess the risk of pseudoaldosteronism for each licorice-containing Kampo formula. We also analyzed the risk factors for pseudoaldosteronism in patients taking yokukansan. Yokukansan (ROR 2.4, 95% confidence interval (CI) 1.9–2.8; p < 0.001) had a higher risk of pseudoaldosteronism than that of other licorice-containing Kampo formulas. Furthermore, the results of a logistic regression analysis in patients taking yokukansan showed that the licorice dose (OR 1.5, 95% CI 1.2–2.0; p < 0.01), older age (<70 years, OR 5.9, 95% CI 1.8–20; p < 0.01), dementia (OR 2.8, 95% CI 1.6–4.9; p < 0.001), low body weight (<50 kg, OR 2.2, 95% CI 1.1–3.5; p = 0.034) were risk factors for pseudoaldosteronism, Although not significant, treatment with loop diuretics (OR 1.8, 95% CI 0.98–3.5; p = 0.059) tended to increase the risk of pseudoaldosteronism. In summary, patients must understand the risk factors when considering taking yokukansan and reduce the licorice dose they consume.

著者

Natsumi Ueda Ryogo Umetsu Junko Abe Yamato Kato Yoko Nakayama Zenichiro Kato Yasutomi Kinosada Mitsuhiro Nakamura

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.38, no.10, pp.1638-1644, 2015-10-01 (Released:2015-10-01)

参考文献数

32

被引用文献数

2 23

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There have been concerns that oseltamivir causes neuropsychiatric adverse events (NPAEs). We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model. NPAE data were obtained from the U.S. Food and Drug Administration Adverse Event Reporting System (2004 to 2013). The lower limit of the reporting odds ratio (ROR) 95% confidence interval (CI) of “abnormal behavior” in Japan, Singapore, and Taiwan was ≥1. The effects of the interaction terms for oseltamivir in male patients aged 10–19 years were statistically significant. The adjusted ROR of “abnormal behavior” was 96.4 (95% CI, 77.5–119.9) in male patients aged 10–19 years treated with osletamivir. In female patients, the results of the likelihood ratio test for “abnormal behavior” were not statistically significant. The adjusted NPAE RORs were increased in male and female patients under the age of 20 years. Oseltamivir use could be associated with “abnormal behavior” in males aged 10–19 years. After considering the causality restraints of the current analysis, further epidemiological studies are recommended.

著者

Masayoshi Kumai Shungo Imai Shintaro Kato Ryo Koyanagi Kenkichi Tsuruga Takehiro Yamada Yoh Takekuma Mitsuru Sugawara

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.4, pp.593-598, 2021-04-01 (Released:2021-04-01)

参考文献数

21

被引用文献数

4

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Nausea is a typical adverse event associated with opioids. In this study, we performed logistic regression analysis with the aim of clarifying the risk factors for nausea induced by extended-release oxycodone (ER-OXY). Furthermore, we constructed a decision tree (DT) model, a typical data mining method, to estimate the risk of oxycodone-induced nausea by combining multiple factors. A retrospective study was conducted on patients who newly received ER-OXY for cancer pain during hospitalization at Hokkaido University Hospital in Japan from April 2015 to March 2018. In logistic regression and DT analyses, the dependent variable was the presence or absence of nausea. Independent variables were the potential risk factors. First, univariate analyses were performed to screen potential factors associated with oxycodone-induced nausea. Then, multivariate and DT analyses were performed using factors with p-values <0.1 in the univariate analysis. Of 267 cases included in this study, nausea was observed in 30.3% (81/267). In multivariate logistic regression analysis, only female sex was extracted as an independent factor affecting nausea (odds ratio, 1.98). In the DT analysis, we additionally revealed that an age <50 years was a risk factor for nausea in female patients. Thus, our DT model indicated that the risk of ER-OXY-induced nausea was highest in the subgroup comprising females <50 years of age (66.7%) and lowest in male patients (25.1%). The DT model suggested that the factor of young women may be an increased risk of ER-OXY-induced nausea.

著者

Maho Tsubota Kazuki Matsui Saaya Fukushi Kyoko Okazaki Fumiko Sekiguchi Atsufumi Kawabata

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.3, pp.461-464, 2021-03-01 (Released:2021-03-01)

参考文献数

23

被引用文献数

6

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T-Type Ca2+ channels (T-channels), particularly Cav3.2, are now considered as therapeutic targets for treatment of intractable pain including visceral pain. Among existing medicines, bepridil, a multi-channel blocker, used for treatment of arrhythmia and angina, and pimozide, a dopamine D2 receptor antagonist, known as a typical antipsychotic, have potent T-channel blocking activity. We thus tested whether bepridil and pimozide could suppress visceral pain in mice. Colonic and bladder pain were induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and systemic administration of cyclophosphamide (CPA), respectively. Referred hyperalgesia was assessed by von Frey test, and colonic hypersensitivity to distension by a volume load with intracolonic water injection and spontaneous bladder pain were evaluated by observing nociceptive behaviors in conscious mice. The mice exhibited referred hyperalgesia and colonic hypersensitivity to distension on day 6 after TNBS treatment. Systemic administration of bepridil at 10–20 mg/kg or pimozide at 0.1–0.5 mg/kg strongly reduced the referred hyperalgesia on the TNBS-induced referred hyperalgesia and colonic hypersensitivity to distension. CPA treatment caused bladder pain-like nociceptive behavior and referred hyperalgesia, which were reversed by bepridil at 10–20 mg/kg or pimozide at 0.5–1 mg/kg. Our data thus suggest that bepridil and pimozide, existing medicines capable of blocking T-channels, are useful for treatment of colonic and bladder pain, and serve as seeds for the development of new medicines for visceral pain treatment.

著者

Nobuhiko Taguchi Minoru Yuriguchi Takuya Ando Ryosuke Kitai Hitomi Aoki Takahiro Kunisada

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.9, pp.1446-1449, 2019-09-01 (Released:2019-09-01)

参考文献数

16

被引用文献数

4 13

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During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.

著者

Yukihiko Aramaki Hidetoshi Arima Mamiko Takahashi Eriko Miyazaki Takatoshi Sakamoto Seishi Tsuchiya

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.10, pp.1461-1466, 2003 (Released:2003-10-01)

参考文献数

23

被引用文献数

4 5

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The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [32P]-labeled phosphodiester oligonucleotide ([32P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontophoretic experiments, isolated hairless mouse skin was used with a horizontal diffusion cell. The enhancing effect of pulse depolarization (PDP) iontophoresis on the [32P]D-oligo permeation through the skin was better, and the skin irritation was less, than those of constant direct current (CDC) iontophoresis. The apparent fluxes of [32P]D-oligo were enhanced with the increasing current densities and [32P]D-oligo concentrations in the donor solution, whereas the enhanced flux decreased with the increasing NaCl concentrations in the donor solution. An optimum electric current was observed for the intradermal delivery of [32P]D-oligo, and intact [32P]D-oligo was detected within the skin after iontophoresis for 6 h. These results suggest that PDP iontophoresis may be useful for the intradermal delivery of antisense oligonucleotides.

著者

Yuichiro Kanno Rumi Ota Kousuke Someya Taichi Kusakabe Keisuke Kato Yoshio Inouye

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.9, pp.1460-1465, 2013-09-01 (Released:2013-09-01)

参考文献数

34

被引用文献数

12 22 1

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The myogenic differentiation of C2C12 myoblast cells is induced by the novel androgen receptor (AR) partial agonist, (17α,20E)-17,20-[(1-methoxyethylidene)bis-(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), as well as by dihydrotestosterone (DHT). YK11 is a selective androgen receptor modulator (SARM), which activates AR without the N/C interaction. In this study, we further investigated the mechanism by which YK11 induces myogenic differentiation of C2C12 cells. The induction of key myogenic regulatory factors (MRFs), such as myogenic differentiation factor (MyoD), myogenic factor 5 (Myf5) and myogenin, was more significant in the presence of YK11 than in the presence of DHT. YK11 treatment of C2C12 cells, but not DHT, induced the expression of follistatin (Fst), and the YK11-mediated myogenic differentiation was reversed by anti-Fst antibody. These results suggest that the induction of Fst is important for the anabolic effect of YK11.

著者

Motoki Imai Fumitaka Kawakami Makoto Kubo Makoto Kanzaki Hiroko Maruyama Rei Kawashima Tatsunori Maekawa Yoshifumi Kurosaki Fumiaki Kojima Takafumi Ichikawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.11, pp.1660-1668, 2020-11-01 (Released:2020-11-01)

参考文献数

44

被引用文献数

5

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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with Parkinson’s disease. LRRK2 is a large protein with multiple functional domains, including a guanosine 5′-triphosphate (GTP)-binding domain and a protein kinase domain. Recent studies indicated that the members of the Rab GTPase family, Rab8a and Rab10, which are involved in the membrane transport of the glucose transporter type 4 (GLUT4) during insulin-dependent glucose uptake, are phosphorylated by LRRK2. However, the physiological role of LRRK2 in the regulation of glucose metabolism is largely unknown. In the present study, we investigated the role of LRRK2 using dexamethasone (DEX)-induced glucose intolerance in mice. LRRK2 knockout (KO) mice exhibited suppressed glucose intolerance, even after treatment with DEX. The phosphorylation of LRRK2, Rab8a and Rab10 was increased in the adipose tissues of DEX-treated wild-type mice. In addition, inhibition of the LRRK2 kinase activity prevented the DEX-induced inhibition of GLUT4 membrane translocation and glucose uptake in cultured 3T3-L1 adipocytes. These results suggest that LRRK2 plays an important role in glucose metabolism in adipose tissues.

著者

Go Ando Kazuaki Taguchi Yuki Enoki Yuta Yokoyama Junko Kizu Kazuaki Matsumoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.11, pp.1799-1804, 2019-11-01 (Released:2019-11-01)

参考文献数

20

被引用文献数

22

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Investigation of the occurrence time of adverse drug reactions helps to prevent the development and aggravation of adverse reactions, but the expression time of ganciclovir-induced adverse events has not been elucidated. In this study, using databases of spontaneous adverse event reports, the Japanese Adverse Drug Event Report database (JADER) and the U.S. Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS), the incidence of adverse reactions due to ganciclovir and their expression time were analyzed. As a result of calculation of the reporting odds ratio (ROR) and 95% confidence interval for individual main adverse reactions of ganciclovir (cytopenia, leukopenia, thrombocytopenia, liver damage, and acute renal failure), a signal was detected for all adverse reactions in both databases, except for liver damage in JADER. Furthermore, the Weibull distribution was performed for the analysis of onset time of each ganciclovir-induced adverse event. The results of Weibull parameter α and β values of each adverse event in both JADER and FAERS suggested that most adverse events occurred within 30 d and classified into the early failure type, except that thrombocytopenia and acute renal failure in JADER classified into the random failure type. Based on these findings, it concluded that the paying attention to signs of each ganciclovir-induced adverse event is required from the early phase after ganciclovir administration. However, in FAERS, development after a long-term course also accounted for 11%, suggesting that long-term periodic monitoring of adverse reactions would be also required.

著者

Katsuyuki Nakamura Toshiaki Tanaka Naoya Masumori Atsushi Miyamoto Takeshi Hirano

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.10, pp.1506-1510, 2020-10-01 (Released:2020-10-01)

参考文献数

24

被引用文献数

7

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The usefulness of the urine protein : creatine ratio (UPCR) in management of molecular targeted therapy and immunotherapy has not been studied, although urine protein dipstick testing (uPr) is widely used in the clinical setting. The aim of this study was to investigate the usefulness of UPCR as compared to uPr in patients undergoing molecular targeted therapy for advanced renal cell carcinoma (RCC). A total of 25 patients (median age 68 years) with advanced RCC were included. Sunitinib, pazopanib, axitinib, sorefenib, everolimus, and nivolumab were administered to 15, 9, 16, 3, 7, and 13 patients, respectively, with duplication. Proteinuria was managed according to the grade determined by UPCR. Data at every treatment visit were retrospectively collected and uPr and UPCR were compared. The overall incidences of any grade of proteinuria associated with sunitinib, pazopanib, axitinib, sorafenib and everolimus were 86.7, 88.9, 93.8, 100, and 85.7%, respectively. There were discordances between the uPr-based grade and UPCR-based grade. UPCR did not meet the criteria of Grade 3 in 70.6, 100, 83.3, and 83.3% at visits in cases with uPr 3+ for sunitinib, pazopanib, sorafenib, and everolimus, respectively. In axitinib treatment, UPCR did not meet the criteria for withholding in 46.2% of the cases of uPr 2+ and more. Our study suggests that UPCR may be useful tool in management of adverse events associated with tyrosine kinase inhibitors, everolimus and can provide patients with optimal opportunities for receiving treatment.

著者

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.43, no.8, pp.1147-1153, 2020-08-01 (Released:2020-08-01)

参考文献数

64

被引用文献数

2

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Gene and nucleic medicines have recently gained attention as novel drugs with the advancement of molecular biology and genetics; however, they have low bioavailability and low target delivery due to their low stability and poor membrane permeability. Therefore, the development of an effective drug delivery system (DDS) is necessary for the practical use of gene and nucleic acid medicines; however, despite considerable research, both safety and efficiency remain poor. Furthermore, the healthcare needs are not met by traditional DDS. Therefore, we developed an effective multi-functional DDS, which is constructed using materials that are safe for human consumption. This DDS involves several ternary complexes as novel gene delivery carriers constructed by coating the cationic complex of the gene and nucleic acid medicines as well as the biodegradable cationic polymer with a biocompatible anionic polymer. Early implementation of the ternary complex in clinical studies is expected due to their efficacy and safety. Furthermore, these complexes may be prepared using large-scale manufacturing. In addition, personalized DDS may be prepared according to the patient’s disease stage, which is useful for advanced therapy.

著者

Shigeru Ishida Hanae Morikawa Hiroyuki Watanabe Toshikazu Tsuji Takeshi Sugio Yasuo Mori Toshihiro Miyamoto Satohiro Masuda Koichi Akashi Nobuaki Egashira

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.3, pp.488-492, 2020-03-01 (Released:2020-03-01)

参考文献数

19

被引用文献数

1

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The intravenous injection of bendamustine often induces venous irritation, which reduces patients’ QOL. We previously reported that the dilution of the final volume of bendamustine from 250 to 500 mL significantly decreased the incidence of venous irritation. However, the influence of this change on the therapeutic efficacy of bendamustine remains unclear. Therefore, the aim of this study was to evaluate the efficacy and safety profiles of bendamustine at different dilutions of the final volume, comparing with the correspondences of previous studies. Thirty-four patients, who received a total of 161 courses of bendamustine and rituximab chemotherapy, were included in this study. The overall response rate of this regimen was 94.1% in this study, which was comparable to that reported in the BRB study (94.2%, a phase II study of bendamustine plus rituximab therapy in Japanese patients). Additionally, the median progression-free survival was not inferior to that reported in the BRB study. Bendamustine-induced venous irritation was observed in 17.6% of the patients during the first treatment cycle administered at a final volume of 500 mL, and was found to be lower than that observed in the control, where bendamustine was administered at a final volume of 250 mL (85.7%). These results suggest that diluting bendamustine to 500 mL, but not to 250 mL, reduces the incidence of venous irritation without a negative impact on its therapeutic efficacy; thus, this simple strategy may be beneficial to ensure efficacy and safety in patients receiving regimens including bendamustine.

著者

Haruka Fujikawa Taise Kawakami Ryunosuke Nakashima Aoi Nasu Shunsuke Kamei Hirofumi Nohara Yuka Eto Keiko Ueno-Shuto Toru Takeo Naomi Nakagata Mary Ann Suico Hirofumi Kai Tsuyoshi Shuto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-01091, (Released:2020-01-31)

参考文献数

36

被引用文献数

9

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Epithelial sodium channel (ENaC) is an amiloride-sensitive sodium ion channel that is expressed in epithelial tissues. ENaC overexpression and/or hyperactivation in airway epithelial cells cause sodium over-absorption and dysregulated ciliary movement for mucus clearance; however, the agents that suppress constitutive airway ENaC activation are yet to be clinically available. Here, we focused on macrolides, which are widely used antibiotics that have many potential immunomodulatory effects. We examined whether macrolides could modulate constitutive ENaC activity and downstream events that typify cystic fibrosis (CF) and chronic obstructive pulmonary diseases (COPD) in in vitro and in vivo models of ENaC overexpression. Treatment of ENaC-overexpressing human bronchial epithelial cells (β/γENaC-16HBE14o- cells) with three macrolides (erythromycin, clarithromycin, azithromycin) confirmed dose-dependent suppression of ENaC function. For in vivo studies, mice harboring airway specific βENaC overexpression (C57BL/6J-βENaC-Tg mice) were treated orally with azithromycin, a well-established antimicrobial agent that has been widely prescribed. Azithromycin treatment modulated pulmonary mechanics, emphysematous phenotype and pulmonary dysfunction. Notably, a lower dose (3 mg kg-1) of azithromycin significantly increased forced expiratory volume in 0.1 second (FEV0.1), an inverse indicator of bronchoconstriction. Although not statistically significant, improvement of pulmonary obstructive parameters such as emphysema and lung dysfunction (FEV0.1%) was observed. Our results demonstrate that macrolides directly attenuate constitutive ENaC function in vitro and may be promising for the treatment of obstructive lung diseases with defective mucociliary clearance, possibly by targeting ENaC hyperactivation.

著者

Yoichi Ishitsuka Yuki Kondo Daisuke Kadowaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.2, pp.195-206, 2020-02-01 (Released:2020-02-01)

参考文献数

154

被引用文献数

29

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Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N-acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar “dark side” of APAP as an otherwise safe analgesic/antipyretic drug.