AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two ...AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.展开更多
Tongguanteng （Marsdenia tenacissima）, which is mainly distributed in the Yunnan and Guizhou provinces of China, wasfirst recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmac...Tongguanteng （Marsdenia tenacissima）, which is mainly distributed in the Yunnan and Guizhou provinces of China, wasfirst recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies,the chemical composition of Tongguanteng （Marsdenia tenacissima） is complex and contains C21 steroidal saponins,polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibitstumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins topromote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascularendothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature,leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxidedismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity andantioxidation in the body. Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor,and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentrationof anti-tumor drugs in tumor cells.展开更多
Sinomenine is widely used in a variety of rheumatic diseases, and more and more attention has been paid to theadverse reaction in allergic reactions, digestive tract, blood, circulatory and nervous system. The applica...Sinomenine is widely used in a variety of rheumatic diseases, and more and more attention has been paid to theadverse reaction in allergic reactions, digestive tract, blood, circulatory and nervous system. The application ofsinomenine in rheumatoid diseases and its side effects were reviewed here, which may provide a reference for thesafe and effective application of sinomenine preparations.展开更多
文摘AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.
文摘Tongguanteng （Marsdenia tenacissima）, which is mainly distributed in the Yunnan and Guizhou provinces of China, wasfirst recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies,the chemical composition of Tongguanteng （Marsdenia tenacissima） is complex and contains C21 steroidal saponins,polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibitstumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins topromote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascularendothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature,leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxidedismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity andantioxidation in the body. Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor,and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentrationof anti-tumor drugs in tumor cells.
文摘Sinomenine is widely used in a variety of rheumatic diseases, and more and more attention has been paid to theadverse reaction in allergic reactions, digestive tract, blood, circulatory and nervous system. The application ofsinomenine in rheumatoid diseases and its side effects were reviewed here, which may provide a reference for thesafe and effective application of sinomenine preparations.
