Adachi, Y.; Sugimoto, M.; Yamada, Y.; Kanda, J.; Yonezawa, A.; Yamagiwa, T.; Hanyu, Y.; Watanabe, M.; Arai, Y.; Mizumoto, C.; Kitawaki, T.; Kondo, T.; Yamashita, K.; Imayoshi, N.; Shigetsura, Y.; Katsube, Y.; Ikuta, K.; Hira, D.; Ikeda, R.; Takaori-Kondo, A.; Nakagawa, S.; Terada, T.

Background Patients undergoing hematopoietic stem cell transplantation (HSCT) often receive multiple antibiotics and antifungal agents concurrently, making it crucial to understand potential pharmacokinetic interactions. We report here an interaction between the glycopeptide antibiotic teicoplanin (TEIC) and sulfo-butyl ether-beta-cyclodextrin (SBECD), a solubilizing excipient in the intravenous formulation of posaconazole (PSCZ). Methods We performed a single-center retrospective analysis of HSCT patients who received oral and intravenous PSCZ during TEIC therapy. Associations between PSCZ administration and TEIC concentration-to-dose (C/D) ratios were evaluated using linear mixed-effects models. In rats, we examined the effects of intravenous PSCZ and SBECD on TEIC pharmacokinetics by assessing the area under the concentration-time curve (AUC) and urinary excretion of total TEIC and its components. Molecular docking and in vitro protein-binding assays were also conducted to investigate the interaction between TEIC and SBECD. Results In HSCT patients, TEIC C/D ratios were significantly lower during intravenous PSCZ administration but not during oral PSCZ use. In rats, both intravenous PSCZ and SBECD decreased TEIC AUC and increased urinary excretion, particularly for the A2 group. Docking simulations indicated that the hydrophobic side chain of TEIC A2-2 fit within the SBECD cavity, and in vitro assays confirmed SBECD concentration-dependent increases in TEIC unbound fractions. Conclusion Co-administration of intravenous PSCZ containing SBECD may reduce TEIC protein binding, thereby enhancing renal elimination.