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Objective:To establish an LC–MS/MS method for the determination of the active metabolite(SN-38) and secondary metabolite(SN-38G) of irinotecan in rat liver microsomes incubation system, and optimize the incubation conditions. Methods:Meth-anol was selected to precipitate protein in the samples, and then the concentrations were analyzed by LC–MS/MS. All the separation was carried out on a ZORBAX Eclipse XDB-C18 column(2. 1 mm × 50 mm, 3. 5 μm) with the mobile phase of acetonitrile – water (containing 0. 1% formic acid) (23 :77) at a flow rate of 0. 3 ml·min-1. The mass spectrometer was operated with multiple reac-tions monitoring ( MRM) using electrospray ionization ( ESI) . The incubation conditions were optimized by single factor design. Re-sults:SN-38 and SN-38G showed a good linearity ( r≥0. 9972) respectively within the range of 2. 3-920 ng·ml-1 and 2. 5-1000 ng ·ml-1. The intra-and inter-day RSD was below 14. 6%(n=6). The average recovery was within the range of 74. 1%-123. 4% with RSD below 13. 5% (n=6). The optimal incubation conditions were as follows:the concentration of liver microsomal protein was 0. 3 mg·ml-1 and the incubation time was 30 min. Conclusion:The method is rapid, sensitive and accurate in the quantification of SN-38 and SN-38G in the incubation system,which provides methodological basis for the activity determination of UGT1A1 enzyme in vitro.
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OBJECTIVE:To establish physiological pharmacokinetic (PBPK) model of cefdinir in healthy volunteers,and to predict pharmacokinetic process of cefdinir in volunteers after oral administration. METHODS:Using“toubao dini”“cefdinir”“logP”“pKa”as keywords,related literatures about physico-chemical constants of cefdinir were retrieved from CNKI,ScienceDi-rect,PubMed and other databases;according to related guidelines and preliminary clinical trial plan of FDA,GastroPlusTM 8.6 soft-ware was used to establish PBPK model of oral administration of cefdinir;the effectiveness of the model was evaluated by multiple error. The model was used to simulate the absorption of cefdinir in the gastrointestinal tracts. The bioequivalence of test preparation and reference preparation were evaluated through single and population(n=500)simulation tests using cmax and AUC0-∞ of cefdinir reference preparation (capsule and granular formulation) as factors when release rate t85%=15 min (i.e. accumulatively released 85% within 15 min). RESULTS:The blood concentration-time curves of cefdinir predicted by PBPK model fitted well with mea-sured value(R2≥0.95);the pharmacokinetic parameters(cmax,tmax,AUC0-∞)were close to measured results,and the multiple er-rors were less than 2. After oral administration,cefdinir was mainly absorbed by the intestinal tract (45.6%),especially by seg-ment 1 of jejunum(14.8%);the absorption amount was significantly lower than the release amount of absorption site,and reached the maximal value(about 40%)within 4 h. The results of single simulation test showed that there was no statistical significance in cmax and AUC0-∞ between cefdinir test and reference preparations (P>0.05). The results of population simulation test showed that the relative bioavailability of cefdinir test particle and test capsule respectively were 99.01%-102.99% and 97.60%-105.90%;90%CI of cmax and AUC0-∞ values were within 80%-125% of reference preparation. CONCLUSIONS:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and bioequivalence evaluation of cefdinir preparations. Test preparation and reference preparation are equivalent.
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Objective To observe the clinical efficacy of surround electroacupuncture in relieving pain after operation for mixed hemorrhoids. Method Seventy-two patients with mixed hemorrhoids were randomized into a treatment group and a control group, 36 cases in each group. The two groups both received the corresponding interventions once in 15 min after the operation: the treatment group received electroacupuncture treatment, and the control group was only placed in a simulated environment of electroacupuncture but without receivimg any needling treatment. The pain intensity was evaluated by using Verbal Rating Scale (VRS), Wong-Baker Faces Pain Rating Scale, and Visual Analogue Scale (VAS) at 11 different time points after the treatment: once every 1 h in 8 h after the treatment, once at the first defecation, once respectively 24 h and 48 h after the treatment. The data were statistically analyzed afterwards. Result At 3 h and 4 h after the treatment and at the first defecation after the treatment, the VRS scores of the treatment group were significantly lower than that of the control group (P<0.05); respectively at 4 h, 5 h, 6 h, 7 h, and 8 h after the treatment and at the first defecation, the Wong-Baker scores of the treatment group were significantly lower than that of the control group (P<0.05); respectively at 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, and 8 h after the treatment, at the first defecation, as well as at 24 h after the treatment, the VAS scores of the treatment group were significantly lower than that of the control group (P<0.05); it indicates that the pain intensity of the treatment group should be lower than that of the control group at the above time points, and the analgesic effect in the treatment group lasts a longer time, running a lower risk of losing effectiveness compared to the control group (P<0.05). Conclusion Real-time acupuncture treatment after the operation is significantly effective in relieving pain after operation for hemorrhoids.
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Objective To investigate the expression and the effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) on lungs of rats with sepsis.Methods Forty Sprague-Dawley (SD) rats were randomly divided into two groups,namely sham group (n =8) and sepsis model group (n =32).The rats of model group were modeled by cecal ligation and puncture (CLP),and were further divided into four subgroups as per the time after modeling,namely 6 h (n =8),12 h (n =8),24 h (n =8),48 h (n =8)subgroups.Blood and lung samples were taken 6 h,12 h,24 h and 48 h after modeling.The histological changes in lungs of the rats were observed under light microscope.Expressions of TIMP-1 mRNA,Bax mRNA and Bcl-2 mRNA in lungs were measured by RT-PCR.The immunohistochemistry was used to label the CD18 in lungs during different phases of sepsis.The data were processed by t test.Results Compared with sham group,the lung tissues of rats in model group were injured to a certain extent after CLP.The expression of TIMP-1 mRNA and the number of CD18 positive cells increased at the same time (P ＜ 0.01),and peaked 24 hours later (P ＜ 0.01).While the expression of Bax mRNA in model group decreased markedly 12-48 hours after modeling (P ＜ 0.01-0.05),and reached minimum 48 hours later (P ＜ 0.01).The expression of Bcl-2 mRNA in model group changed unnoticeable.The positive correlation between variations in number of CD18 positive cells and expression of TIMP-1 mRNA was found in model group (r =0.426,P ＜ 0.01).Conclusions The increase in expression of TIMP-1 mRNA in lungs is closely associated with the lung injury of sepsis.The mechanism of lung injury is likely attributed to the preservation of inflammatory cells from apoptosis,and the persistent inflammation response causes tissue damage,leading to organ dysfunction.
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OBJECTIVES: To assess the efficacy of Fuhuang Tablets in treating internal hemorrhoid hemorrhage and discussing the design and quality control of clinical trials of traditional Chinese medicine. METHODS: According to two-center, randomized, blinded and controlled study, 144 patients with internal hemorrhoids were divided into 2 groups. Seventy-two patients were treated with Fuhuang Tablets (4 tablets t.i.d. per os) and the other 72 patients were treated with Zhining Tablets (4 tablets t.i.d. per os). Symptoms and signs of the patients were recorded and evaluated at the third and seventh day of treatment respectively. RESULTS: At the third day of treatment, the overall response rates of Fuhuang Tablets-treated group and Zhining Tablets-treated group were 58.57% and 27.78% respectively, with statistic difference between the two groups (P<0.05). At the seventh day of treatment, the overall response rates of Fuhuang Tablets-treated group and Zhining Tablets-treated group were 91.43% and 81.94% respectively, with no statistic difference between the two groups. The laboratory test results and life signs of the 144 patients were normal before and after the treatment. CONCLUSION: Fuhuang Tablets are effective and safe in treating internal hemorrhoid hemorrhage.