کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5547775 | 1556145 | 2017 | 9 صفحه PDF | دانلود رایگان |
pH-dependent solubility - permeability profiles offer a simple way to predict bioavailability after oral application, if bioavailability is only solubility and permeability driven. Combining both pH-dependent solubility and pH-dependent permeability in one diagram provides a pH-window (= ÎpHsol-perm) from which the conditions for optimal oral bioavailability can be taken. The size of this window is directly proportional to the observed oral bioavailability. A set of 21 compounds, with known absolute human oral bioavailability, was used to establish this correlation. Compounds with ÎpHsol-perm < 2 exhibit poor oral bioavailability (< 25%). An increase of ÎpHsol-perm by one pH-unit increases oral bioavailability typically by approximately 25%. For compounds where ÎpHsol-perm â¥Â 3 but still showing poor bioavailability, most probably other pharmacokinetic aspects (e.g. high clearance), are limiting exposure. Interestingly, the location of this pH-window seems to have a negligible influence on the observed oral bioavailability. In scenarios, where the bioavailability is impaired by certain factors, like for example proton pump inhibitor co-medication or food intake, the exact position of this pH-window might be beneficial for understanding the root cause.
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Journal: European Journal of Pharmaceutical Sciences - Volume 105, 15 July 2017, Pages 82-90