Ren Shuyue, Jiao Lingtai, Yang Shiying, Zhang Li, Song Junke, Yu Haoying, Wang Jingrong, Lv Tingting, Sun Lan, Lu Yang, Du Guanhua
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 1 Xian Nong Tan Street, Beijing 100050, China.
Pharmaceutics. 2020 Sep 23;12(10):906. doi: 10.3390/pharmaceutics12100906.
Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.
贝沙罗汀（BEX）是一种特定的维甲酸X受体（RXR）激动剂，已获得美国食品药品监督管理局（FDA）批准用于T细胞淋巴瘤的临床治疗，目前发现它在神经系统中发挥药理作用，但其低生物利用度和较差的脑内分布限制了它在神经系统疾病治疗中的应用。药物共晶是提高活性药物成分（API）生物利用度和组织分布的一种有效方法。在此，构建了一种新型的贝沙罗汀-川芎嗪共晶体系（2BEX-LIG），其中BEX为API，该共晶体系具有令人满意的稳定性和增强的溶解性。检测了BEX的药代动力学特征，结果表明，与给予等量BEX的大鼠相比，给予2BEX-LIG的大鼠中BEX的绝对生物利用度从22.89%提高到42.86%，脑内浓度增加了3.4倍。因此，我们目前的研究表明，新型共晶2BEX-LIG有助于提高BEX的口服生物利用度和脑内分布，从而为脑肿瘤和其他神经系统疾病的临床应用提供显著优势
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