In order to evaluate whether the di

In order to evaluate whether the dissolution advantage of the cocrystal can translate into an oral bioavailability strength, the in vivo bioavailability investigations were performed on INH-SYA cocrystal and physical mixtures of the INH and SYA (equimolar ratio). The serum concentration profiles are shown in Fig. 8, and its corresponding pharmacokinetic parameters determined by PKSolver software are illustrated in Table 1. It is evident from Fig. 8a that the SYA concentrationin the physical mixture showed very low plasma concentration, due to its poor solubility. However, the SYA contents in the cocrystal exhibited favorable pharmacokinetic profiles, revealing that the physicochemical properties of SYA have been optimized by playing the INH's advantages through cocrystal formation. The improved pharmacokinetic performances of the SYA in the INH-SYA cocrystal can be further proved by the parameters of pharmacokinetic listed in Table 1. It shows that the AUC and CMAX of SYA in INH-SYA cocrystal were 3.66-fold and 2.76-fold, respectively, which was significantly higher than those of SYA in the mixture. These observations indicated that the bioavailability of SYA has been effectively enhanced through cocrystal formation. Moreover, the TMAX of SYA in the cocrystal was advanced from 0.75 to 0.50 h, illustrating that the cocrystallization of INH with SYA can accelerate the absorption of SYA. On the other hand, as viewed from Fig. 8b and Table 1, although the peak of plasma concentration and the absorption rate of INH decreased due to cocrystal formation, the FREL still kept at 1.95. That means the bioavailability of INH in the cocrystal does not reduce affected by the decrease in its solubility, and has certain improvement, which may be because of the sustained release of the cocrystal. In summary, the INH-SYA cocrystal displayed optimized and synergistic in vivo pharmacokinetic properties contrast with the physical mixture, which created favorable conditions for overcoming the serious hepatotoxicity of INH as follows.

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结果 (简体中文) 1: [复制]

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为了评估共晶的溶解优势是否可以转化为口服 生物利用度，对INH-SYA 共晶以及INH和SYA的物理混合物（等摩尔比）进行了体内生物利用度研究。血清浓度 曲线如图8所示，其对应的药代动力学参数由 PKSolver软件确定于表1。从图8a可以明显看出， 物理混合物中的SYA浓度由于血浆浓度而非常低。溶解性差。然而， 共晶中的SYA含量显示出良好的药代动力学特征，表明 通过 共晶形成发挥INH的优势，可以优化SYA的理化特性。 表1中列出的药代动力学参数可以进一步证明SYA在INH-SYA 共结晶中的改善的药代动力学性能。结果表明， INH-SYA共结晶中SYA的AUC和CMAX为3.66倍和2.76倍，分别 显着高于混合物中的SYA。这些观察结果表明， 通过共晶形成有效地提高了SYA的生物利用度。此外， 共晶中SYA的TMAX从0.75升高到0.50 h，说明 INH与SYA 的共结晶可以加速SYA的吸收。另一方面，作为 从图8b和表1 可以看出，尽管由于共晶形成，血浆浓度的峰值和INH 的吸收率降低，但FREL仍保持在1.95。这意味着 共晶中INH 的生物利用度不会因其溶解度的降低而降低，而是会有所改善，这可能是由于共晶的持续释放所致。在 摘要中，INH-SYA共晶体显示的优化和体内药代动力学协同 与物理混合物，其创造了有利条件用于克服性能对比 INH的严重肝毒性如下。

正在翻译中..

结果 (简体中文) 2:[复制]

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In order to evaluate whether the dissolution advantage of the cocrystal can translate into an oral bioavailability strength, the in vivo bioavailability investigations were performed on INH-SYA cocrystal and physical mixtures of the INH and SYA (equimolar ratio). The serum concentration profiles are shown in Fig. 8, and its corresponding pharmacokinetic parameters determined by PKSolver software are illustrated in Table 1. It is evident from Fig. 8a that the SYA concentration in the physical mixture showed very low plasma concentration, due to its poor solubility. However, the SYA contents in the cocrystal exhibited favorable pharmacokinetic profiles, revealing that the physicochemical properties of SYA have been optimized by playing the INH's advantages through cocrystal formation. The improved pharmacokinetic performances of the SYA in the INH-SYA cocrystal can be further proved by the parameters of pharmacokinetic listed in Table 1. It shows that the AUC and CMAX of SYA in INH-SYA cocrystal were 3.66-fold and 2.76-fold, respectively, which was significantly higher than those of SYA in the mixture. These observations indicated that the bioavailability of SYA has been effectively enhanced through cocrystal formation. Moreover, the TMAX of SYA in the cocrystal was advanced from 0.75 to 0.50 h, illustrating that the cocrystallization of INH with SYA can accelerate the absorption of SYA. On the other hand, as viewed from Fig. 8b and Table 1, although the peak of plasma concentration and the absorption rate of INH decreased due to cocrystal formation, the FREL still kept at 1.95. That means the bioavailability of INH in the cocrystal does not reduce affected by the decrease in its solubility, and has certain improvement, which may be because of the sustained release of the cocrystal. In summary, the INH-SYA cocrystal displayed optimized and synergistic in vivo pharmacokinetic properties contrast with the physical mixture, which created favorable conditions for overcoming the serious hepatotoxicity of INH as follows.

正在翻译中..

结果 (简体中文) 3:[复制]

复制成功！

为了评估共晶体的溶解优势是否可以转化为口服 生物利用度强度，对INH-SYA进行体内生物利用度研究 INH和SYA的共晶和物理混合物（等摩尔比）。血清浓度 如图8所示，其相应的药代动力学参数由 PKSolver软件如表1所示。从图8a可以明显看出，SYA浓度 由于溶解度差，物理混合物中的血浆浓度很低。然而， 共晶中的SYA含量显示出良好的药代动力学曲线，表明 通过发挥INH的优势，优化了SYA的理化性质 共晶形成。SYA在INH-SYA中的药动学性能改进 表1所列的药代动力学参数可进一步证明共晶。它表明 在INH-SYA共晶中SYA的AUC和CMAX分别为3.66倍和2.76倍， 明显高于混合物中的SYA。这些观察结果表明 通过共晶的形成有效地提高了SYA的生物利用度。而且， SYA在共晶中的TMAX由0.75提高到0.50h，说明 INH与SYA共晶可以加速SYA的吸收。另一方面，作为 从图8b和表1来看，尽管血浆浓度和吸收率的峰值 由于共晶形成，INH下降，FREL仍保持在1.95。也就是说 INH在共晶中的生物利用度不受溶解度降低的影响而降低，并有一定的提高，这可能是由于共晶的缓释作用所致。在 总之，INH-SYA共晶在体内的药代动力学表现出优化和协同作用 与物理混合物相比，其特性为克服 INH的严重肝毒性如下。

正在翻译中..

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