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This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
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Aim To establish a LC-MS/MS method for determination of 5-HT, NE, DA and observe the con-centration of 5-HT, NE, DA in rat plasma of CUMS. Methods Twenty-two male SD rats were divided into control group and model group. Model group was given 9 kinds chronic unpredictable mild stimulating factors every day. 21 days later, behavior and orbital blood were measured before and after modeling. Using benzo-yl chloride as a pre-column derivatization reagent, three analytes and IS were derivatized before LC-MS/MS detection. Change in three kinds of neurotransmit-ter concentration was measured in rat plasma before and after modeling. Results After modeling, com-pared with control group, the weight of rats in model group was declined significantly ( P<0. 05 ) . Horizon-tal scores, vertical scores and sugar consumption were declined significantly ( P <0. 01 ) . Calibration curves of 5-HT, NE, DA were linear between 1. 47 ~752, 1. 75 ~898 , 2. 05 ~1 053 μg · L-1 and LOQ were 1. 47, 1. 75, 2. 046μg·L-1 ,respectively. The recov-ery of 5-HT, NE, DA from plasma was over than 70%, and RSD of inter-day and intra-day assay was limited in 15%. Compared with control group, the con-centration of 5-HT, NE, DA in rat plasma of model group was declined to ( 3. 99 ± 1. 21 ) , ( 6. 24 ± 1. 94), (6. 07 ± 1. 98) μg·L-1(P <0. 01). Con-clusion After making CUMS model of depression, three kinds of neurotransmitters in rat plasma are de-creased.
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Aim To investigate the pharmacokinetic effect of aspirin on caffeic acid in dengzhanxixin injec-tion( DI) . Methods Concentration of caffeic acid in rat plasma was detected by LC-MS/MS after rats were given intravenous administration of DI or DI combined with aspirin by gavage. Pharmacokinetic parameters were calculated by DAS 1. 0 pharmacokinetic software. Results In vivo pharmacokinetic models of caffeic acid were two-compartment open models in both the caffeic acid group and the caffeic acid combined with aspirin group. After compatibility, caffeic acid showed a significant increase in T 12β, with a slight decrease in CL. Conclusions Aspirin can reduce metabolic process of caffeic acid in vivo.
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<p><b>OBJECTIVE</b>To detect pharmacokinetics of Danshensu Sodium in Danshen dripping solution in Beagles.</p><p><b>METHOD</b>Danshen dripping solution was dripped intravenously into healthy Beagles at a dose of 10 mL x kg(-1). Their plasma samples were extracted with acetic ether, the blood concentrations were determined by HPLC method.</p><p><b>RESULT</b>Danshensu Sodium showed a good linear relationship within the range of 0.225-18.000 mg x L(-1), with the lowest detectable limit of 0.113 mg x L(-1). Its pharmacokinetic parameters were as follows: tmax was 30 min, Cmax was (9.5742 +/- 2.3715) mg x L(-1), t1/2 was (19.23 +/- 2.97) min, CL was (0.0127 +/- 0.0030) L x min(-1) x kg(-1), AUC(0-tn) was (474.954 +/- 95.483) mg x min x L(-1) and AUC(0-infinity) was (482.494 +/- 95.353) mg x min x L(-1).</p><p><b>CONCLUSION</b>The accurate, stable and reliable blood concentration method shows a one-compartment mode of Danshensu Sodium in Beagles.</p>
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Animals , Dogs , Female , Male , Chromatography, High Pressure Liquid , Drug Stability , Drugs, Chinese Herbal , Pharmacokinetics , Lactates , Pharmacokinetics , SolutionsABSTRACT
Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.
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<p><b>OBJECTIVE</b>To establish a LC-MS-MS method for quantification of cinnamic acid in human plasma and study its pharmacokinetics after administration of Mailuoning injection at a single and the multiple doses to healthy volunteers.</p><p><b>METHOD</b>Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate-ether. Cinnamic acid was determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (45: 55) at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 146.8 /103.1 [M - H]- for cinnamic acid and m/z 245.6 /126.0 [M - H] - for tinidazole (IS). After administration of Mailuoning injection at a single and the multiple doses via intravenous guttae (ivgtt) to 10 healthy volunteers, the concentration of cinnamic acid in plasma was determined by LC-MS-MS method. The concentration-time curves were simulated by DASver 1.0 and the pharmacokinetic parameters were calculated.</p><p><b>RESULT</b>The calibration curve was linear within the range of 0.5400 microg x L(-1). The LLOQ was 0.5 microg x L(-1) and RSDs of intra and inter day were less than 10%. The concentration-time curves of cinnamic acid were consistent with the two-compartment model. The pharmacokinetic parameters after administration of Mailuoning Injection at a single and the multiple injections were as follows: C(max) (microg x L(-1)), 115.73 +/- 44.31 and 113.79 +/- 25.61; T1/2beta (h), 0.41 +/- 0.087 and 0.52 +/- 0.132; V(L x kg(-1)), 0.519 +/- 0.134 and 0.651 +/- 0.322; CL(L x kg(-1) x h(-1)), 0.899 +/- 0.295 and 0.830 +/- 0.222; AUC(0-tn) (microg x L(-1) x h), 158.64 +/- 56.019 and 166.49 +/- 46.788.</p><p><b>CONCLUSION</b>The developed LC-MS/MS method was sensitive and selective, and there was no interference from endogenous substances. After administration of Mailuoning injection via ivgtt to healthy volunteers, the pharmacokinetic parameters of cinnamic acid between a single and the multiple doses, and between the male and female were no significant difference. There was no accumulation with multiple injections for cinnamic acid, but there were significant individual differences in the pharmacokinetics of cinnamic acid in volunteers.</p>
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Adult , Female , Humans , Male , Young Adult , Chromatography, High Pressure Liquid , Methods , Cinnamates , Blood , Pharmacokinetics , Drugs, Chinese Herbal , Injections , Tandem Mass Spectrometry , MethodsABSTRACT
OBJECTIVE: To prepare compound ornidazole gel and conduct its quality control. METHODS: The gel was prepared with 0.6% carbopol - 940 as base and with ornidazole and cimetidine as main ingredients. Contents of 2 constituents were determined directely by UV - spectrophotometry. The stability of the finished product was investigated as well. RE-SULTS:The gel obtained was good in appearance, shaping and spreading. The linear ranges for ornidazole and cimetidine were all 0.5-32uuuuuuuuuug/ ml. The average recovery rates of ornidazole and cimetidine were 100.58% (RSD= 1.17%) and 100.59% (RSD=1.61%), respectively. The stability investigation results were in line with the requirement of Chinese Pharmacopeia 2000 version. CONCLUSION:The formula of compound gel is reasonable; its preparation technics is simple and the quality is reliable; and which meets the requirements of clinical medication.
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0.05).CONCLUSION:It is more economical to use domestic CsA in liver transplantation recipients.
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Objective Albumin is well known to decrease in response to sepsis, However, the.degradation and distribution in patients with severe sepsis to explore the mechanism of hypoalbuminemia in sepsis. Methods 10 volunteers and 10 patients with severe sepsis. 125I labeled albumin was administered intravenously to 10 healthy volunteers and 10 patients with severe sepsis. Each subject had frequent blood samples taken at 0,1,2,4,8,12,24 hours and on day 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 18, 22, 25 to measure 125I concentration and draw the curve of concentration over time. Plasma was regarded as the central pool and body fluid as side pool, The curve of albumin concentration vs time was expected to follow two compartment model. Results Radioactivity of blood samples was counted and the results were graphically expressed. The half-life time(t1/2), apparent volume of distribution(Vd) and transportation rate(K12) of albumin from the central pool to the side pool were calculated. The half-life time in sepsis was obviously shorter than that in control group (8.2 1.4 vs 12.5 1.7days, P<0.001). The transportation rate in sepsis group was quicklier than that in control group [(4.4±1.9)× 10-2/h vs (2.4±0.6)×10-2/h, P<0.005]. There was no significant difference in apparent volume of distribution between two groups. Conclusions In patients with severe sepsis, the distribution rate of albumin from plasma to body fluid was obviously elevated and the decomposition rate of albumin was markedly increased.
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0.05).Conclusion When given concomitantly as a Cocktail,theophylline,chlorzoxazone and dapsone have no pharmacokinetic interaction,which could be used together to evaluate CYP1A2,CYP2E1 and CYP3A4 activity.
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AIM:To research the absorption mechanism of aesculin across Caco-2 monolayer model.METHODS:The Caco-2 cell monolayers drug transport model was assigned to study the double transport mechanism of aesculin to explore the absorption of aesculin according as time and drug concentration determined through HPLC and the P_ app was calcalated.RESULTS:In the Caco-2 monolayer model,the transport of aesculin form Apical to Basolateral was similar to the transport form basolateral to apical.CONCLUSION:The main mechanism of the aesculin intestinal absorption in the Caco-2 monolayer model is passive transference.
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The effects of different technicological processes on the dissolubility of enteric coating aspirin tablets were studied. With testing in vitro, significant differences were found among three kinds of tablets from four factories in dissoluble feature. The length of time needed for release and that for disintegration of tablets from Factory C were 90 minutes and 5 minutes repectively, which were the shortest,and those from Factocy B, 210 minutes and 120 minutes repectively,which were the longest among three kinds of tablets. The average dissoluble amount of aspirin contained in tablets from Factory C was 74.07％;Factory D,74. 51％; Factory A, 66.6％; and Factory B, 62.51％. All the parameters determined were statistically different among three kinds of products by analysis of varianee(p