Two kinds of Ipriflavone tablets (IP) were orally cross administered to 8 healthy volunteers. The serum level of IP at different time was determined by HPLC, 3P87 pharmacokinetic package was used in the analysis of ...Two kinds of Ipriflavone tablets (IP) were orally cross administered to 8 healthy volunteers. The serum level of IP at different time was determined by HPLC, 3P87 pharmacokinetic package was used in the analysis of the time course of serum concentration and it had shown that the data well fitted a 2 compartment model. Pharmacokinetic parameters and area under curve (AUC) were calculated. The relative bioavailability of Tabellae IP made in China vs that made in Japan (as a reference) was 1.003( P >0.05). The values of AUC T max and C max of the two preparations were also comparable by the statistical analysis, so they were bioequivalent.展开更多
Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of ...Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results: It was reported that rifabutin co-administration altered pharmacokinetics of 97/63(active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were(4.03 ± 0.60) and(5.44 ± 1.15) μg·h·m L-1 upon 97/78 administration alone, while the values were decreased to(1.13 ± 0.10) and(1.23 ± 1.13) μg·h·m L-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. Conclusions: It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with the invitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.展开更多
文摘Two kinds of Ipriflavone tablets (IP) were orally cross administered to 8 healthy volunteers. The serum level of IP at different time was determined by HPLC, 3P87 pharmacokinetic package was used in the analysis of the time course of serum concentration and it had shown that the data well fitted a 2 compartment model. Pharmacokinetic parameters and area under curve (AUC) were calculated. The relative bioavailability of Tabellae IP made in China vs that made in Japan (as a reference) was 1.003( P >0.05). The values of AUC T max and C max of the two preparations were also comparable by the statistical analysis, so they were bioequivalent.
基金the Council for Scientific and Industrial Research (CSIR),India,for providing research fellowships
文摘Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results: It was reported that rifabutin co-administration altered pharmacokinetics of 97/63(active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were(4.03 ± 0.60) and(5.44 ± 1.15) μg·h·m L-1 upon 97/78 administration alone, while the values were decreased to(1.13 ± 0.10) and(1.23 ± 1.13) μg·h·m L-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. Conclusions: It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with the invitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.
