- 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
- 2
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.