Use of mouse model in pharmacokinetic studies of poorly water soluble drugs: Application to fenofibrate

Fenofibrate has recently been used as drug model in several studies with the objective of optimizing the development of some drug delivery systems to overcome the problem of poor aqueous solubility of the newly discovered API. The adequacy of the drug delivery systems to improve the oral bioavailability of encapsulated drug is generally evaluated by a pharmacokinetic study. The use of mouse as animal model for pharmacokinetic studies has become more important in the last decade because of many similarities with the human model in terms of the mechanisms of absorption, metabolism and elimination. Nevertheless, the mouse is often hampered by the very small volumes of blood that could be obtained during sampling. The aim of this work was to overcome the problem of lower volumes of plasma withdrawn by developing an appropriate protocol for sample preparation and a suitable HPLC method for drug quantification in mouse plasma. Linear calibration curve was obtained over the concentration range from 0,16 μg/mL to 32 μg/mL (r2 = 0,9999) with LLOQ of 0,16 μg/mL The RSD in both intra-run and inter-run precision study was less than 11% and the extraction recoveries were above 91.9%. The reproducible method was successfully applied to the pharmacokinetic study of fénofibrate in mouse.

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