کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2481931 1556239 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Human serum binding and its effect on the pharmacodynamics of the lantibiotic MU1140
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Human serum binding and its effect on the pharmacodynamics of the lantibiotic MU1140
چکیده انگلیسی

The degree of MU1140 binding to human serum was measured and the effect of serum on MU1140 pharmacodynamics against Streptococcus pneumoniae and Staphylococcus aureus was investigated. 92.7% ± 2.0% of total MU1140 was bound to serum components as determined by ultrafiltration when tested in the concentration range 6.25–200 μg/ml.MIC and time-kill studies were used to study the effect of serum on the dynamics of MU1140. Serum inhibited MU1140 activity against S. pneumoniae but was found to enhance its activity against S. aureus. This phenomenon has not been reported for any other lantibiotic. Time-kill studies of MU1140 against S. aureus in various concentrations of serum revealed that the greatest bactericidal effect was observed at the lowest serum concentration.Mathematical modeling was used to quantify serum augmentation of MU1140 activity against S. aureus. Serum, at the lowest concentration, was shown to decrease MU1140 EC50 against S. aureus by an order of magnitude.The data suggests that unbound MU1140 comprise the pharmacologically active fraction. Further, these findings suggest the possible existence of a complex dual inhibition and augmentation effect of serum on MU1140's activity against S. aureus. The molecular mechanism responsible for the synergistic action of human serum on MU1140's activity against S. aureus remains to be elucidated.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 41, Issue 5, 23 December 2010, Pages 658–664
نویسندگان
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