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Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.

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Purpose: This study aims to compare the effects and prognosis of medical thoracoscopy-assisted argon plasma coagulation (APC) combined with electrosurgical unit (ESU) surgery, video-assisted thoracic surgery (VATS), and pleurodesis surgery, in providing appropriate treatment for elderly refractory pneumothorax patients.Methods: Patients with refractory pneumothorax aged over 65 years were divided into three groups: APC combined with ESU (N = 20), VATS (N = 26), and pleurodesis (N = 24). Data on demographic characteristics, lung function evaluation, and short- and long-term prognoses were collected.Results: Following surgery, compared with the APC-ESU and pleurodesis groups, patients in the VATS group demonstrated poor short-term prognoses, with high pleural effusion drainage levels and high visual analog scores (VAS; P <0.05). After the surgery, St. George’s Respiratory Questionnaire (SGRQ) scores in the pleurodesis group were slightly elevated, whereas SGRQ scores in both the APC-ESU and VATS groups demonstrated a continual decrease. Finally, medical resource consumption analysis demonstrated a significant difference in hospitalization costs among the three groups; the VATS group being the most expensive.Conclusion: Medical thoracoscopy-assisted APC combined with ESU is a safe, effective, and affordable treatment for elderly patients with refractory pneumothorax.