Editorial: Benefit and risk on drug-drug interactions in infections

Hideo Kato ^1* Nobuhiro Asai ² Mao Hagihara ²

• ¹ Department of Clinical Pharmaceutics, Mie University Graduate School of Medicine, Mie, Japan
• ² Aichi Medical University, Nagakute, Aichi, Japan

Alternation in the efficacy or toxicity of one medication due to the presence of another simultaneously administered medication can be frequent, which is called drug-drug interactions (DDIs). Since clinically relevant DDIs are mainly associated with absorption, distribution, metabolism and excretion process of each medication in the body as well as the interactions between various medications in the body, in-depth understanding of the pharmacokinetic or pharmacodynamic processes can enhance antimicrobial effect, prevent incidence of antimicrobial resistance, and reduce adverse events. However, the information on DDIs is not enough in clinical trials, and the process of Isavuconazole is a new extended-spectrum triazol for a treatment of invasive aspergillosis.Isavuconazole is a moderate inhibitor of CYP3A4 with fewer DDIs than voriconazole. Therefore, metabolic profiles of various CYP3A4 substrates have been reported at the combined therapy with isavuconazole. However, despite the requirement for a transition between azole antifungals due to toxicity in clinical settings, a report on changes in the blood cyclosporine level at transitioning from voriconazole to isavuconazole is limited. Shiraishi et al. illustrated one case showing the effect of switching from voriconazole to isavuconazole on the blood cyclosporine level. Moreover, a PBPK model simulation was conducted to assess the potential interactions between isavuconazole and cyclosporine and between voriconazole and cyclosporine. Finally, the adverse events associated with cyclosporine when combined with voriconazole or isavuconazole using the FDA Adverse Event Spontaneous Reporting System (FAERS) database was investigated. In a case report, the blood cyclosporine level decreased by more than half After switching from voriconazole to isavuconazole.Considering the inhibitory effects on the gastrointestinal tract, a PBPK analysis estimated that isavuconazole increased the area under the curve and Cmax of cyclosporine by 1.48-fold and 1.84fold, respectively, although assuming no change in gastrointestinal metabolism, these effects were minimal. The FAERS database included 9,144 reports on cyclosporine and 174 on cyclosporine with voriconazole, but none concomitant with isavuconazole. The interaction of isavuconazole with cyclosporine was weaker than that with voriconazole. Maintaining a two-hour dosing interval between isavuconazole and cyclosporine may minimize gastrointestinal drug interactions.The hybrid FowlTα1 peptide represents a biomolecule synthesized from Fowlicidins (Fowl) and Thymosin α1 (α1). This peptide exhibits remarkable anti-inflammatory and antimicrobial properties.Ahmad et al. investigated supplemental effects of the peptide to interact with lipopolysaccharide (LPS).In LPS-stimulated macrophages, the hybrid FowlTα1 peptide significantly reduced the release of nitric oxide, tumor necrosis-alpha, interleukin-6 (IL-6), and IL-1β in a dose-dependent manner and displayed robust antimicrobial activity against Escherichia coli compared to conventional antibiotic. The findings of the study highlighted the potential of the FowlTα1 peptide as a novel therapeutic agent for antimicrobial, anti-inflammatory, and anti-endotoxin applications.In conclusion, this Research Topic provides valuable knowledge and information on the benefit and risk on DDIs in infections. Understanding the DDIs in infections can help effective strategies to promote optimal use for enhancing the drug efficacy as well as preventing the emergence of drug resistance of bacteria.