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OBJECTIVE To investigate the effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats. METHODS SD rats were randomly divided into 4 groups according to single-dose administration and multiple-dose administration， with 6 rats in each group. Groups A and B were given olanzapine （5 mg/kg） or olanzapine （5 mg/kg）+Yiru tiaojing granules （0.972 g/kg） in a single gavage， and groups C and D were administered with the same method once a day for 14 d. Blood was collected from the orbital venous plexus before administration and 5， 15， 30 min and 1， 2， 3， 6， 8， 12， 24 h after the last administration， respectively. The blood concentration was determined by LC-MS， and the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS Compared with group A， group B showed a significant decrease in AUC0－24 h， AUC0－∞ and cmax （P＜0.05）， and a significant prolongation of MRT0－24 h， MRT0－∞ and CLz/F （P＜0.05）； there was no statistically significant difference in the pharmacokinetic parameters between group C and group D （P＞0.05）. CONCLUSIONS A single administration of Yiru tiaojing granules can inhibit the absorption of olanzapine in rats， and long-term administration of Yiru tiaojing granules does not have a significant effect on the pharmacokinetic process of olanzapine.
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Objective To investigate the effect of procyanidin on permeability of rodamin 123(R123)and fluorescein sodium (FS)via different intestinal mucosa in rat. Methods The cumulative permeability and the apparent permeability cofficient(Papp)of R123 and FS via rat intestinal membranes at the procyanidin concentration of 20 mg/L was evaluated by the method of Ussing Cham?ber. The concentrations of R123 and FS in the receptor samples were determined by fluorospectrophotometry. Results The absorptive directed permeability of R123 across all membranes was increased by co-administration of procyanidins,whereas that of the secretive direct was decreased. Compared with control group,the secretive directed permeability of R123 was significantly decreased in colon (P<0.01). Conclusion Procyanidin could inhibit the secretion of R123 on different intestinal mucosa which might be related to the inhibition of P-gp function.
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OBJECTIVE:To study the dermal pharmacokinetic difference of triptolide in normal and diabetic rats,and to pro-vide reference for rational drug use in the clinic. METHODS:12 Wistar rats were randomly divided into normal group and diabetic model group(0.1%streptozotocin intraperitoneally),with 6 rats in each group. Both group were given Triptolide cream 0.5 g to ab-dominal skin,and dialysate was collected by microdialysis every 30 min for consecutive 12 h. Subcutaneous concentration was de-tected by HPLC-MS,and subcutaneous concentration-time curves were analyzed and compared between two groups,and Winnon-lin 5.0.1 software was used to calculate pharmacokinetic parameters. RESULTS:The pharmacokinetic parameters of normal group and diabetic model group were that cmax were(1.54±0.37)and(5.12±1.34)μg/ml;tmax were(7.32±0.24)and(6.21±0.35)h;AUC0-12 h were (12.65 ± 4.64) and (37.43 ± 5.23)μg·h/ml,with statistical significance (P<0.05). CONCLUSIONS:The change of dermal structure caused by diabetes can increase percutaneous penetration amount of triptolide in rats,and drug dosage should be reduced according to circumstances so as to reduce side effects.
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Objective To investigate the effect of expression of microRNA-27a(miR-27a) and microRNA-451(miR-451) in A2780/T cells and its relativity to multidrug resistance (MDR)1 mRNA inhibition by procyanidin. Methods Stem-loop PCR method was performed to evaluate the expression of miR-27a and miR-451 in use of procyanidin (0-40μmol/L) in 0-48 h in A2780/T cells. Additionally, over-expressing or interfecting microRNAs by using mimics or inhibitor of miR-27a and miR-451, the expression of MDR1 mRNA was assessed by RT-PCR in cells exposing to procyanidin. Results The expression of miR-27a and miR-451 was significant inhibited by procyanidin in both time- and concentration-dependency. Over-expressed MDR1 mRNA associated with miR-27a or miR-451 mimics was blocked by procyanidin, whereas there was no effect on down-expressed MDR1 mRNA associated with miR-27a or miR-451 inhibitor by procyanidin. Conclusion Procyanidin inhibits MDR1 mRNA expression by inhibiting miR-27a and miR-451 expression in A2780/T cells.
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<p><b>OBJECTIVE</b>To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats.</p><p><b>METHODS</b>The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp).</p><p><b>RESULTS</b>Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected.</p><p><b>CONCLUSION</b>Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.</p>