ABSTRACT
Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
ABSTRACT
Objective: To observe the effect of Cinnamomi Ramulus on the distribution kinetics of ephedrine (E) and pseudoephedrine (PE) from Ephedrae Herba in brain tissues of mice. Methods: Mice were ig adminstered by Cinnamomi Ramulus and codecoction of Cinnamomi Ramulus combined with Ephedrae Herba. Brain tissues of mice were collected at different time after drug administration. The variation of E and PE with time was determined by GC-MS method. The non compartmental kinetic was fitted and the parameters were calculated by Kinetica 5.0.11 software, so as to evaluate the effect of Cinnamomi Ramulus on the distribution kinetics of E and PE from Ephedrae Herba in brain tissues of mice. Results: Compared with the Ephedrae Herba group, in the group with the codecoction of Cinnamomi Ramulus combined with Ephedrae Herba, the tmax of E and PE distributed in the brain tissues of mice was delayed, the AUC0-∞ of E and PE in the brain tissues of mice under the drug concentration curve was smaller and the MRT0-∞ of E was reduced. Conclusion: Cinnamomi Ramulus combined with Ephedrae Herba has the propertis of delaying the distribution process of E and PE, reducing the cumulative distribution volume, and accelerating the elimination of E and PE in the brain tissues of mice. Above all, Cinnamomi Ramulus can relieve the neurotoxicity of Ephedrae Herba, and there is the combination function of mutual restraint and mutual supression between the two drugs.
ABSTRACT
Objective To observe the meridian tropism of Polygoni Avicularis Herba by tissue distribution of avicularin in rats.Methods Tissue distribution of avicularin in rat following a single iv administration was appointed and observed.HPLC method was established and validated for the determination of avicularin in rat tissues.Results Kidney and bladder were the most important target tissue of avicularin.Conclusion HPLC method is successfully applied to tissues distribution study of avicularin after iv administration to rats,and the results explain Polygoni Avicularis Herba on bladder tropism reasonably.