کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10162577 1114334 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Determination of Atypical Nonlinear Plasma-Protein-Binding Behavior of Tigecycline Using an In Vitro Microdialysis Technique
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Determination of Atypical Nonlinear Plasma-Protein-Binding Behavior of Tigecycline Using an In Vitro Microdialysis Technique
چکیده انگلیسی
Tigecycline, a novel glycylcycline antibiotic, shows atypical nonlinear plasma-protein-binding behavior using ultrafiltration and ultracentrifugation techniques. The mechanism of such counterintuitive behavior is currently unknown. Ultrafiltration and ultracentrifugation cause fractional change in protein concentration and therefore may influence plasma-protein binding. Microdialysis (MD), a novel technique, can sample unbound drugs without any change in fractional protein concentration. To determine whether the atypical nonlinear plasma-protein-binding behavior is not related to measurement technique, the plasma-protein binding of tigecycline was determined using MD. A sensitive liquid chromatography-mass spectrometry method was developed and validated for the bioanalysis of tigecycline in the dialysate. The probe recoveries and plasma-protein binding of tigecycline at four different concentration levels 0.1, 1, 10, and 100 μg/mL were determined. Similar to ultracentrifugation and ultrafiltration, MD also showed atypical nonlinear plasma-protein-binding behavior of tigecycline up to 10 μg/mL, but unbound fraction increased at 100 μg/mL indicating saturation of mechanism responsible for atypical nonlinear behavior. This study concludes that the atypical nonlinear binding behavior of tigecycline is not technique-dependent, rather it is a true behavior of tigecycline. Further investigations are necessary to elucidate the mechanism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 3, March 2014, Pages 1013-1019
نویسندگان
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