著者

Yuya Matsuda Shunsaku Nakagawa Ikuko Yano Satohiro Masuda Satoshi Imai Atsushi Yonezawa Takashi Yamamoto Mitsuhiro Sugimoto Masahiro Tsuda Tetsunori Tsuzuki Tomohiro Omura Takayuki Nakagawa Toyofumi Fengshi Chen-Yoshikawa Miki Nagao Hiroshi Date 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.4, pp.397-402, 2022-04-01 (Released:2022-04-01)

参考文献数

24

被引用文献数

3

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Invasive Aspergillus infection is a major factor for poor prognosis in patients receiving lung transplantation (LT). An antifungal agent, itraconazole (ITCZ), that has antimicrobial activity against Aspergillus species, is used as a prophylactic agent against Aspergillus infection after LT. ITCZ and its metabolite, hydroxyitraconazole (OH-ITCZ), potently inhibit CYP3A and P-glycoprotein that metabolize or excrete calcineurin inhibitors (CNIs), which are the first-line immunosuppressants used after LT; thus, concomitant use of ITCZ and CNIs could induce an increase in the blood concentration of CNIs. However, no criteria for dose reduction of CNIs upon concomitant use with ITCZ in LT recipients have been defined. In this study, the effect of ITCZ and OH-ITCZ on the blood concentrations of two CNIs, tacrolimus and cyclosporine, after LT were retrospectively evaluated. A total of 39 patients who received LT were evaluated. Effects of ITCZ and OH-ITCZ on the concentration/dosage (C/D) ratio of tacrolimus and cyclosporine were analyzed using linear mixed-effects models. The plasma concentrations of OH-ITCZ were about 2.5-fold higher than those of ITCZ. Moreover, there was a significant correlation between the plasma concentrations of ITCZ and OH-ITCZ. Based on parameters obtained in the linear regression analysis, the C/D ratios of cyclosporine and tacrolimus increase by an average of 2.25- and 2.70-fold, respectively, when the total plasma concentration of ITCZ plus OH-ITCZ is 1000 ng/mL. In conclusion, the plasma levels of ITCZ and OH-ITCZ could be key factors in drawing up the criterion for dose reduction of CNIs.

著者

Miko Kondo Shunsaku Nakagawa Satoru Orii Kotaro Itohara Mitsuhiro Sugimoto Tomohiro Omura Yuki Sato Satoshi Imai Atsushi Yonezawa 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.43, no.10, pp.1463-1468, 2020-10-01 (Released:2020-10-01)

参考文献数

34

被引用文献数

1

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Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive infections. For adult patients, treatment with vancomycin requires effective therapeutic drug-monitoring (TDM) to achieve clinical outcomes and reduce the incidence of adverse effects. However, it remains still unclear whether the TDM with vancomycin is beneficial in yielding better clinical outcomes in pediatrics. The objective of our study was to evaluate whether the clinical response to treatment was associated with initial trough concentrations of vancomycin in pediatric patients. A retrospective observation study of 60 patients (age: 1 month–15 years) who had completed and qualified for analysis was conducted at Kyoto University Hospital. The response to treatment was assessed by the time to resolution of fever and time to 50% decline in C-reactive protein (CRP). In addition, we explored whether vancomycin trough level was associated with the baseline characteristics. Trend analysis showed that there were significant correlations between vancomycin trough level and age, body weight, estimated glomerular filtration rate, and serum albumin levels. The time to resolution of fever of the patients with higher initial trough level (≥ 5 µg/mL) was significantly lower than that of the patients with lower trough level (< 5 µg/mL). The higher vancomycin concentration tended to be associated with the shorter time to 50% decline in CRP. The findings suggest that initial trough concentration is important in achieving better outcomes with vancomycin treatment in pediatrics.

著者

Congyun Jin Yoshiaki Yao Atsushi Yonezawa Satoshi Imai Hiroki Yoshimatsu Yuki Otani Tomohiro Omura Shunsaku Nakagawa 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.40, no.11, pp.1990-1995, 2017-11-01 (Released:2017-11-01)

参考文献数

22

被引用文献数

13

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Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase.