ABSTRACT
A rapid, sensitive and specific analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of thalidomide concentration in human plasma. The analyte and internal standard were extracted by liquid-liquid extraction with ether-dichloromethane (3:2, v/v) and separated on a TC-C(18) column using methanol-10 mM ammonium acetate-formic acid (60:40:0.04, v/v/v) as the mobile phase at a flow rate of 0.9 ml/min. The detection was performed using an API 4000 triple quadrupole mass spectrometer in the positive electrospray ionization (ESI) mode and completed within 3.0 min. The multiple reaction monitoring (MRM) transitions were m/z 259.1â84.0 for the analyte and m/z 195.9â138.9 for temozolomide. The calibration curve exhibited a linear dynamic range of 2-1500 ng/ml (r>0.9991). The intra-and inter-day precisions (as relative standard deviation; RSD) were 6.8-13.5% and 4.3-5.0% respectively and the accuracy (as relative error; RE) was 2.0-3.5%. The recoveries and matrix effects were satisfactory in all the biological matrices examined. This method was successfully used in a pharmacokinetic study of thalidomide in healthy male volunteers receiving an oral administration of a 200-mg dose.
ABSTRACT
BACKGROUND AND OBJECTIVE: Caspofungin, a novel echinocandin compound, has been approved for the treatment of esophageal and suspected invasive candidiasis and as salvage therapy for invasive aspergillosis. The aim of this study was to assess the efficacy and safety of caspofungin for the prophylaxis and treatment of fungal infections, compared with other medications. METHODS: PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) of caspofungin. Nine RCTs were included in this meta-analysis, performed using Review Manager Version 5.0. Analyses of favorable response, microbiological response, mortality rate, survival rate, relapse rate, and adverse events were performed to evaluate caspofungin. RESULTS: Caspofungin produced similar effects in favorable response rate [relative risk (RR) = 1.07, 95% confidence interval (CI) 0.98-1.17], microbiological response rate (RR = 1.02, 95%CI 0.90-1.15), mortality rate (RR = 0.98, 95%CI 0.78-1.24), survival rate after 7-day follow-up (RR = 1.00, 95% CI 0.91-1.10), and relapse rate (RR =1.18, 95% CI 0.81-1.73) compared with other antifungal agents in the prophylaxis and treatment of patients with fungal infections, particularly those caused by Candida. There were significant differences in clinical and laboratory adverse events between caspofungin and other antifungal agents in favor of caspofungin (RR = 0.66, 95% CI 0.49-0.89) (RR = 0.66, 95% CI 0.57-0.75). CONCLUSION: This meta-analysis shows that caspofungin can be used as effectively as other antifungal agents for prophylaxis and treatment of fungal infections, mainly for Candida, and that it is associated with fewer adverse effects than comparable agents.
Subject(s)
Antifungal Agents/therapeutic use , Echinocandins/therapeutic use , Mycoses/drug therapy , Adolescent , Adult , Antifungal Agents/adverse effects , Caspofungin , Data Interpretation, Statistical , Echinocandins/adverse effects , Follow-Up Studies , Humans , Lipopeptides , Mycoses/microbiology , Mycoses/mortality , Randomized Controlled Trials as Topic , Recurrence , Survival , Treatment OutcomeABSTRACT
The objective of this paper was to investigate the in vitro effects of fusidic acid combined with fosfomycin against methicillin-resistant Staphylococcus aureus (MRSA). In all, 196 MRSA strains isolated from three clinical specimens of human infections from hospitals in China were used in this study. The checkerboard method was used to determine whether combinations act synergistically against these strains. The susceptibility results for fusidic acid and fosfomycin were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. The combination of fusidic acid and fosfomycin demonstrated the following interactions: 87.76% (172/196) synergism, 12.24% (24/196) indifference and no antagonism was seen (minimum and maximum fractional inhibitory concentration index 0.14 and 0.75, respectively). Thus, combinations of fusidic acid and fosfomycin show synergism for most of the MRSA isolates tested in this study, and may be a future therapeutic alternative for infections caused by MRSA.
