Objective: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of selinexor was established to investigate the effects of isavuconazole, itraconazole and fluconazole on the pharmacokinetics of selinexor in rats, respectively.
Methods: Twenty-four healthy male rats were randomly divided into four groups: group A, normal saline; group B, isavuconazole (20 mg/kg); group C, itraconazole (20 mg/kg); and group D, fluconazole (20 mg/kg). After 30 min of oral administration of normal saline, isavuconazole, itraconazole, and fluconazole, all the rats were given selinexor (8 mg/kg). The plasma concentration of selinexor was estimated by UPLC-MS/MS, and the pharmacokinetic parameters of selinexor were calculated by Drug and Statistics (DAS) 2.0 software.
Results: Under these experimental conditions, the method showed good linearity and stability. Intraday and interday accuracy and sample recovery were acceptable. Compared with group A, the C, AUC and AUC of selinexor in group B increased by 59.05%, 31.69%, and 31.45%; the C, AUC and AUC of selinexor in group C increased by 56.14%, 25.34%, and 25.08%; the C, AUC and AUC of selinexor in group D increased by 43.44%, 29.16%, and 31.96%, respectively. The T of the experimental groups were extended, and CLz/F was also significantly reduced.
Conclusion: These results indicated that isavuconazole, itraconazole, and fluconazole have significant inhibitory effects on selinexor pharmacokinetics and increased selinexor plasma exposure in rats. Therefore, when these drugs were used in combination, clinicians should pay attention to the changes in treatment effects and the occurrence of adverse reactions caused by the drug-drug interactions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506178 | PMC |
| http://dx.doi.org/10.2147/IDR.S269831 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Emerging Antifungal Resistance in : Insights from Susceptibility Profiling and Genetic Mutation Analysis.
Emerg Microbes Infect
January 2025
Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China.
species, the leading cause of dermatophytosis globally, are increasingly resistant to antifungal treatments, concerns about effective management strategies. In light of the absence of established resistance criteria for terbinafine and azoles, coupled with a dearth of research on resistance mechanisms in , antifungal susceptibility and drug resistance gene diversity were analyzed across 64 , 65 , and 2 isolates collected in China between 2001 and 2024 and 101 published strains. Analyses of the minimum inhibitory concentrations (MICs) of terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole revealed a concerning increase in with terbinafine resistance, including two novel isolates from China.
View Article and Find Full Text PDFPhaeohyphomycosis Due to Verruconis gallopava: Rare Indolent Pulmonary Infection or Severe Cerebral Fungal Disease?
Mycopathologia
November 2024
Laboratoire de Parasitologie-Mycologie, Service de Parasitologie-Mycologie, AP-HP, Hôpital Saint-Louis, Université Paris-Cité, 1 Avenue Claude Vellefaux, 75010, Paris, France.
Introduction: Phaeohyphomycoses are uncommon and poorly understood opportunistic fungal infections, characterized by a wide spectrum of clinical manifestations ranging from localized skin lesions to disseminated disease. Most frequent genera are Alternaria, Cladophialophora, Exophiala or Curvularia. Less common ones, such as Verruconis gallopava, initially described as responsible of encephalitis of turkeys, pose significant challenges for diagnosis and treatment.
View Article and Find Full Text PDFMultiparametric LC-MS/MS method for simultaneous determination of eleven antifungal drugs and metabolites in human plasma.
J Pharm Biomed Anal
January 2025
Department of Pharmacology, Montpellier University Hospital, Avenue du Doyen Gaston Giraud, Montpellier 34090, France; Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), INSERM, University Montpellier, Montpellier 34090, France. Electronic address:
Article Synopsis
- A new liquid chromatography-tandem mass spectrometry method has been created to measure 11 antifungal drugs and their metabolites in human plasma, essential for monitoring treatment in immunocompromised patients with fungal infections.
- * This method not only optimizes settings and preparation techniques for accurate detection but also follows strict FDA and EMA guidelines to ensure reliability and performance.
- * With a quick processing time of 5 minutes per sample and minimal plasma requirement, this method supports better antifungal therapy management in critical care settings.
Evaluation of the Activity of Triazoles Against Non- and Cryptic Species Causing Invasive Infections Tested in the SENTRY Program.
Open Forum Infect Dis
November 2024
JMI Laboratories, North Liberty, Iowa, USA.
Article Synopsis
- The study evaluated the effectiveness of isavuconazole and other triazoles against 390 non-AFM isolates causing invasive aspergillosis, collected from 41 hospitals between 2017-2021.
- Isavuconazole demonstrated significant antifungal activity, with minimum inhibitory concentrations (MIC) ranging from ≤0.12 to 2 mg/L across different sections of isolates, while some isolates exhibited elevated MIC values.
- Overall, isavuconazole showed potent in vitro activity against non-AFM fungi, though effectiveness varied among and within cryptic species, similar to other triazoles like voriconazole and posaconazole.
Non-Zoonotic Transmission of Sporotrichosis: A Translational Study of Forty-Three Cases in a Zoonotic Hyperendemic Area.
J Fungi (Basel)
August 2024
Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, Brazil.
Article Synopsis
- Zoonotic sporotrichosis, primarily transmitted by cats, has become highly prevalent in Rio de Janeiro, with a study focusing on 43 non-zoonotic cases revealing important epidemiological and clinical data.
- The majority of patients were male and common sources of infection included injuries from plants and soil contact, with a specific fungal species being predominantly responsible for the infections.
- Antifungal susceptibility tests showed some strains resistant to treatment, highlighting the need for ongoing monitoring of antifungal resistance and further investigation into the environmental factors contributing to sporotrichosis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!