ABSTRACT
An LC-MS/MS method was developed for the simultaneous determination of fosaprepitant and aprepitant in human plasma, and applied to a pharmacokinetic study of 150 mg fosaprepitant dimeglumine injection to 12 Chinese healthy volunteers. The analytes and internal standards were extracted from plasma by protein precipitation with acetonitrile and separated on a Cortex C18+ (50 mm×2.1 mm, 2.7 μm) column using a gradient elution procedure. Mass spectrometry was performed in negative MRM mode, and parent-to-produce transitions were as follows:m/z 613.1→78.9 for fosaprepitant, m/z 617.0→78.9 for d4-fosaprepitant, m/z 533.2→275.1 for aprepitant and m/z 537.2→279.1 for d4-aprepitant. Plasma sample was basified to stabilize fosaprepitant. The standard curves were demonstrated to be liner in the range of 15.0 to 6 000 ng·mL-1 for fosaprepitant and 10.0 to 4 000 ng·mL-1 for aprepitant. The intra-day precisions and inter-day precisions and accuracy were within the acceptable limits for all concentrations.
ABSTRACT
Neurokinin I receptor antagonist (NK1RA) fosaprepitant is a new antiemetic drug. Fosaprepitant dimeglumine was ap-proved by FDA in January 2008, while it is still in the approval stage in China. Fosaprepitant, as a prodrug of aprepitant, is rapidly converted to aprepitant after intravenous administration in vivo. The indication of fosaprepitant is the prevention of chemotherapy in-duced nausea and vomiting ( CINV) , especially the delayed CINV. Fosaprepitant as a unique intravenous preparation overcomes the drawbacks of aprepitant with oral administration only. Its bioavailability is not affected by the vomiting of patients. It is also suitable for patients with oral mucositis, who are unfavorable for oral medication. The action mechanisms, pharmacokinetics, and clinical trials of fosaprepitant were reviewed in the paper.
ABSTRACT
Objective:To establish an HPLC method for the determination of calcium disodium edetate in fosaprepitant dimeglu-mine for injection. Methods:The chromatographic column was Agilent Zorbax Eclipse XDB C18(250 mm ×4.6 mm,5μm). The mo-bile phase consisted of 0. 2% tetrabutylammonium hydroxide(adjusting pH to 4. 0 with phosphoric acid)-acetonitrile(85∶15). The flow rate was 1. 0 ml·min-1 . The detection wavelength was 254 nm. The chromatographic column temperature was 35℃. The injection volume was 20μl. Results:The calibration curve was linear within the range of 26. 06-104. 24μg·ml-1(r=0. 999 8) for calcium di-sodium edetate. The average recovery was 99. 51% (RSD=0. 25%, n=9). Conclusion: The method is simple, rapid, accurate, specific and reproducible, and can be used in the determination of calcium disodium edetate in fosaprepitant dimeglumine for injection.
ABSTRACT
Context: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian patients. Aims: This post hoc study assessed the efficacy and safety of fosaprepitant compared with aprepitant for prevention of CINV in the Indian population. A subgroup analysis was performed from data collected in a phase 3 study of intravenous (IV) fosaprepitant or oral aprepitant, plus the 5-HT 3 antagonist ondansetron and the corticosteroid dexamethasone, in cisplatin-naοve patients with solid malignancies. Materials and Methods: Patients scheduled to receive cisplatin (≥70 mg/m 2 ) were administered a single IV dose of fosaprepitant dimeglumine (150 mg) on day 1 or a 3-day dosing regimen of oral aprepitant (day 1:125 mg, days 2 and 3:80 mg) with standard doses of ondansetron and dexamethasone. Patients recorded nausea and/or vomiting episodes and their use of rescue medication and were monitored for adverse events (AEs) and tolerability. Statistical Analysis Used: Differences in response rates between fosaprepitant and aprepitant were calculated using the Miettinen and Nurminen method. Results: In the Indian subpopulation (n = 372), efficacy was similar for patients in both the fosaprepitant or aprepitant groups; complete response in the overall, acute, and delayed phases and no vomiting in all phases were approximately 4 percentage points higher in the fosaprepitant group compared with the aprepitant group. Fosaprepitant was generally well-tolerated; common AEs were similar to oral aprepitant. Conclusions: IV fosaprepitant is as safe and effective as oral aprepitant in the Indian subpopulation and offers an alternative to the oral formulation.