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AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C
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OBJECTIVE:To establish the method for simultaneous determination of tenacissoside A,tenacissoside H and tenacissoside I in Marsdenia tenacissima. METHODS:UPLC-MS/MS method was adopted. The determination was performed on a Phenomenex Kinetex XB-C18column with mobile phase consisted of 0.1% formic acid solution-acetonitrile(gradient elution)at the flow rate of 0.2 mL/min. The column temperature was set at 40 ℃,and sample size was 5 μ L. Multiple reaction monitoring (MRM)mode was adopted with electrospray ion source as ion source,using positive ion scanning. Source jet voltage was 5 500 V,nebulizer pressure was 60 psi,heating pressure was 60 psi,curtain pressure was 20 psi and cone temp was set at 600 ℃. RESULTS:The linear ranges of tenacissoside A,tenacissoside H and tenacissoside I were 0.1-10 ng/mL(r=0.999 7),0.025-10 ng/mL(r=0.999 5),0.025-10 ng/mL(r=0.998 9),respectively;limited of quantation were 0.1,0.025,0.025 ng/mL,limited of detection were 0.05,0.012 5,0.012 5 ng/mL,respectively;RSDs of precision,stability and reproducibility tests were<4.0%. The recoveries were 97.67%-99.00%(RSD=0.47%,n=6),95.00%-101.67%(RSD=2.59%,n=6),96.67%-103.33%(RSD=2.83%, n=6). CONCLUSIONS:The method is simple,precise,stable and reproducible,and can be used for simultaneous determination of tenacissoside A,tenacissoside H and tenacissoside I in M.tenacissima.
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Objective Objective To evaluate the effects and safety of total glucosides of paeony (TGP) in the treatment of patients with Sjogren syndrome.Methods The Cochrane Library,PubMed,EMBASE,CBM,VIP,CNKI,Wanfang databases were searched from their establishments up to September 30,2015.We used the method recommended by the Cochrane collaboration to perform a meta-analysis of randomized controlled trails (RCTs) of total glucosides of peony in the treatment of patients with Sjogren syndrome.Two reviewers analyzed these data independently.The Cochrane Collaboration's software RevMan 5.3 was used for meta-analysis.Results A total of 573 patients in 10 studies were finally included,and were divided into different subgroups.The results of subgroup-analysis showed that:①Schimer test:TGP group had a higher effective rate than the blank control group [MD=2.41,95%CI (0.08,4.74)],lower effective rate than Chinese herbal medicine [MD=-2.55,95%CI (-3.88,-1.22);②Salivary flow:TGP group had a lower effective rate than the control group [SMD=-0.87,95%CI (-1.20,-0.54)].③Rheumatic factors (RF):TGP group had a higher effective rate than Chinese herbal medicine [SMD=0.44,95%CI (0.06,0.82)] and Chinese patent drug [SMD=0.74,95%CI (0.36,1.12)],lower effective rate than the blank control group [SMD=2.23,95%CI (-2.79,-1.67);④ C-reactive protein (CRP):TGP group had a higher effective rate than the control group [MD=4.51,95%CI (1.75,7.26)];⑤IgG:TGP group had a higher effective rate than Chinese patent drug group [MD=2.73,95%CI (1.63,3.84)],lower effective rate than the blank control group [MD=-3.90,95%CI (-5.67,-2.13),but no statistical difference was noted when compared with Chinese herbal medicine and Western medicine groups;⑥ESR:TGP group had a higher effective rate than Chinese herbal medicine group [MD=12.73,95%CI (3.62,21.84)] and Chinese patent drug group [MD=7.82,95%CI (5.39,10.24)],lower effective rate than the blank control group [MD=-7.13,95%CI (-12.70,-1.56) and Western medicine group [MD=-12.19,95%CI (-24.19,-0.19)];⑦Safety:8 studies reported adverse effects in 41 patients.TGP group had a higher adverse reaction rate than the control group [OR=3.23,95%CI (1.60,6.50)].Conclusion Current evidence demonstrates that TGP can effectively improve CRP,but its effects on Salivary flow,Schimer test,IgG,ESR,RF were not significant.However,the heterogeneity and high risk of bias in the reports involved in this study limits the reliability of this conclusion.
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Objective To investigate the effects of different doses of dexmedetomidine on the minimum alveolar concentration (MAC) of sevoflurane required to inhibit the body movement evoked by skin incision.Methods ASA Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,with body mass index of 21-27 kg/m2,undegoing elective lower abdominal surgery under general anesthesia,were randomly divided into 4 groups:control group (group C) and different doses of dexmedetomidine groups (groups D1,D2 and D3 ).Dexmedetomidine 0.2,0.4 and 0.6 μg/kg in 15 ml of normal saline was infused over 30 min before induction of anesthesia in groups D1,D2 and D3 respectively.While 15 ml of normal saline was given instead in group C.Anesthesia was induced with inhalation of 8％ sevoflurane.The patients were mechanically ventilated after tracheal intubation.Anesthesia was maintained with inhalation of sevoflurane.The initial end-tidal concentration of sevoflurane was set at 3.0％,3.0％,2.5％,2.0％ in groups C,D1,D2 and D3 respectively.The ratio between the two successive concentrations was 0.9.Skin incision was made after 15 min of equilibratiton.At least 7 independent crossover pairs were observed in each group.The MAC of sevoflurane was the mean of the end-tidal concentration of sevoflurane of each crossover pair,and 95 ％ confidence interval (CI) was calculated.Results In groups C,D1,D2 and D3,18,20,20 and 22 patients were enrolled respectively.The MAC (95 ％ CI) of sevoflurane was 2.5 ％ (2.3 ％-2.8 ％ ),1.5 ％ ( 1.3 ％-1.7％),1.3％ (1.0％-1.6％) and 1.1％ (0.7％-1.5％) in groupsC,D1,D2 and D3 respectively.The MAC of sevoflurane was significantly lower in groups D1,D2,D3 than in group C,and in groups D2 and D3 than in group D1 ( P ＜ 0.05).There was no significant difference in the MAC of sevoflurane between groups D2 and D3 ( P ＞0.05).Conclusion Dexmedetomidine 0.2,0.4,0.6 μg/kg can significantly decrease the MAC of sevoflurane required to inhibit the body movement evoked by skin incision in a dose-dependent manner.
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This paper reported that a new type of floating osmotic pump of ambroxol hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.