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??OBJECTIVE To report a clinical case and review the therapy of renal anemia in children with EPO-?? non-response to provide ideas on optimization of dosing regimens and new ways of clinical practice. METHODS One case of renal anemia was described and analyzed, and relevant literature was accessed and reviewed. RESULTS The level of hemoglobin increased to 100 g??L^-1 and the clinical symptoms were alleviated after transfering to EPO-?? from EPO-??. CONCLUSION For pediatric patients with chronic renal anemia, EPO-?? instead of EPO-?? is effective.     

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??OBJECTIVE To construct a novel daunorubicin-loaded microparticles (DNR-MPs)drug delivery system, and study its proliferation inhibiton effect on leukemia cells. METHODS Both DNR-MPs-IDL(DNR microparticles with intracellular drug loading method)and DNR-MPs-EDL (DNR microparticles with extracellular drug loading method)were prepared from HL-60 cells, and the average particle size, Zeta potential and drug loading efficiency of DNR-MPs were measured. The uptake of DNR-MPs by HL-60 cells was analyzed by confocal laser scanning microscopy (CLSM)and flow cytometry (FCM). The inhibition effect of DNR-MPs on the proliferation of HL-60 cells was evaluated by MTT assay. RESULTS There was no significant difference in the average particle size and Zeta potential of the two DNR-MPs. The drug loading efficiency of DNR-MPs-EDL was higher compared with DNR-MPs-IDL. The uptake RESULTS showed that the two DNR-MPs significantly increased the drug uptake compared with free DNR (P<0.05). DNR-MPs-IDL showed a higher drug uptake by the cells than DNR-MPs-EDL did (P<0.05). They also exhibited an enhanced inhibition effect on the proliferation of HL-60 cells compared with DNR (P<0.05). CONCLUSION The different ways of preparation of drug-loaded microparticles can cause varying anti-tumor effect. Microparticles can significantly augment the anti-leukemia efficacy of DNR, indicating a promising drug carrier for the therapy of leukemia.     

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??OBJECTIVE To investigate drug-induced liver injury(DILI) in clinical pathway on patients with breast cancer and colorectal cancer and to explore whether the prophylactic use of hepatoprotective drugs can be included in the clinical pathway. METHODS Two hundred and five cases from January 2015 to March 2017 were selected. The patients were divided into two groups according to the prophylactic use of hepatoprotective drug. The incidence, time, severity and outcome of DILI, prophylactic use of hepatoprotective drugs were investigated. DILI related risk factors were screened and analyzed by logistic linear regression to discuss the necessity and opportunity of prophylactic use of hepatoprotective drugs. RESULTS Forty-three(20.98%) patients without DILI had prophylactic use of hepatoprotective drugs in 205 cases. The incidence of DILI in the non-prophylactic group was 4.88%. Both two groups hadn't occurred DILI during the first and second cycles of chemotherapy. However, there was a statistically significant difference in the rate of DILI between the prophylactic and non-prophylactic use of hepatoprotective drugs groups in the third cycles of chemotherapy(P<0.05). Multifactor analysis showed that prophylactic use of hepatoprotective drugs was a protective factor for the DILI. CONCLUSION The liver function should be reinforced during the first and second cycles of chemotherapy. The hepatoprotective drugs could be used prophylactically before the next period of chemotherapy if patient with abnormal liver function.     

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??OBJECTIVE To analyze the microbial contamination and investigate the bacteriostatic efficacy of compound balloonflowers and ephedrine syrup(??). METHODS The compound balloonflowers and ephedrine syrup(??) was analyzed for the bacteriostatic efficacy, content of bacteriostatic agent and C₁₈ column was adopted with gradient elution. The mobile phase consisted of 0.02 mol??L^-1 ammonium acetate solution and methanol. The detective wavelength was set at 255 nm. The contaminating bacteria detected in the samples were identified by VITEK2 Campact, MALDI-TOF-MS and 16S rRNA sequencing, and homology analysis was conducted for the contaminating bacteria in the samples from the same enterprise. RESULTS The bacteriostatic efficacy of the products of one enterprise did not meet the requirements of Chinese Pharmacopoeia(2015 edition). There were excessive and uneven contamination of microorganisms in the samples. The dosages of bacteriostatic agents in some enterprises did not conform to the standard requirements. CONCLUSION Production enterprises should strictly control the dosages of bacteriostatic agents and the stability of the production process, and strengthen the monitoring of the sterilization effect of the whole production process to improve product quality.     

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??OBJECTIVE To observe the influence of safflower yellow(SY) on inflammatory injury in cortex of APP/PS1 double Alzheimer??s disease(AD) transgenic mice.METHODS Six-month-old APP/PS1 transgenic male mice were used in the study.The mice were randomly divided into five groupsmodel group, galanthamine group,high,middle and low dose groups of Safflower Yellow,and wild-type mice with same age were selected into normal control group. Each group mice were performed Morris water maze test after given different drugs by gavage for three months. The level of IL-1??, IL-4, IL-10, IFN-?? and iNOS in cortex were detected by ELISA. RESULTS Compared with wild-type controls, the ability of learning and memory were decreased in the model group. The level of IL-1??, IFN-?? and iNOS increased as well as the expression of IL-4, IL-10 decreased(P<0.01). After SY treatment, the learning and memory abilities of middle dose group were elevated (P<0.01); it could obviously down-regulate the expression of IL-1??, IFN-??, iNOS and up-regulate the expression of IL-4 and IL-10 (P<0.01). High and low dose groups could obviously down-regulate the expression of IFN-??, iNOS and up-regulate the expression of IL-10 (P<0.01). High dose group does had obvious effect of up-regulating the expression of IL-4 (P<0.01), Both of High and low dose groups didn??t have statistical significance on the expression of IL-1??.CONCLUSION Safflower Yellow could improve the ability of learning and memory and exert protective effects on inflammation damage in the cortex of APP/PS1 transgenic mice.     

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??OBJECTIVE To establish a method for determination of diclofenac sodium in human plasma under high-fat meal condition using two-dimensional liquid chromatography (2D-HPLC) coupled with trapping column, and to evaluate the bioequivalence and the bioavailability of diclofenac sodium sustain-released tablets in healthy volunteers. METHODS Under fed state, eighteen healthy male volunteers were divided into two groups by an open, randomized two period crossover design with a single dose of diclofenac sodium sustain-released tablets. The plasma concentrations were determined by 2D-HPLC method, and calculated pharmacokinetic parameters and bioavailability. RESULTS The main pharmacokinetic parameters of test and reference preparations after a single dose were: AUC_0??16 was (2 591.6 ?? 705.8 ) and (2 588.8??772.0) ng??h??mL^-1;AUC_0????was (2 896.4??839.7) and (2 700.3??806.1) ng??h??mL^-1; t_max was (4.6??0.7) and (4.4??0.9)h; ??_max was(1 332.8??912.5) and (1 325.7??706.3) ng??mL^-1, respectively. The relative bioavailability of test preparation in single dose was (102.4??15.1)%. CONCLUSION The 2D-HPLC method coupled with trapping column is a simple, rapid and specific for determination of diclofenac sodium in human plasma. The RESULTS of statistical analysis indicate that the two preparations are bioequivalent in healthy volunteers with a single dose under high-fat fed condition.     

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??OBJECTIVE To prepare and characterize paroxetine resinate, and evaluate the in vitro drug release rate and taste-masking effect. METHODS A full factorial design was first conceived and applied to screen some process and formulation parameters (reaction temperature, stirring speed, drug concentration in solution and the ratio of resin to drug) on the key responses of resinationprocess, such as drug utilization ratio, drug loading and complexation constant. The paroxetine resinate was then characterized and evaluated by scanning electronic microscope (SEM), differential scanning calorimetry (DSC), in vitro drug release test and panel test of taste-masking. RESULTS The resin/drug ratio and reaction temperature were identified as the most important factors on paroxetine resinate preparation.The drug-resin complex was successfully formed via ion exchange mechanism rather than physical absorption with complete in vitro drug release (>96%) in acidic or salt solution and good taste-masking effect.CONCLUSION Paroxetine resinate with good performance can be prepared via optimization of process and formulation parameters, which will facilitate the development of generic paroxetine suspension.     

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??OBJECTIVE To compare the chemical composition and therapeutic effect between Prunella vulgaris L stem leaf and ear, thus to provide evidence for judging whether the stem leaf of Prunella vulgaris L can substitute the ear as an herbal medicine. METHODS Aqueous extracts of the stem leaf and ear of Prunella vulgaris L from different producing areas were analyzed with HPLC-ESI-MSⁿ. The anti-inflammatory effects were observed by inflammatory models of ear edema induced by dimethylbenzene in mice and hind paw edema induced by carrageenan in rats.Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma level of TNF-?? and antioxidant activities were detected by ABTS method. RESULTS Prunella vulgaris L stem leaf and ear were not significantly different in chemical composition, both of which contained mainly triterpenoids, flavonoids, phenolic acids and other substances. Compared with the model group, Prunella vulgaris L ear significantly reduced the hind paw edema in rats induced by carrageenan from 1 h after oral administration (P<0.05), while the onset time of stem leaf was later than 1 h.Both groups could significantly reduce the ear edema in mice induced by dimethylbenzene(P<0.01). The TNF-?? levels in the Prunella vulgaris L stem leaf and ear groups [(24.16??1.24) and (24.33??2.36 )ng??mL^-1] were lower than that in the model group [(31.34??1.94) ng??mL^-1] (P<0.01).Prunella vulgaris L stem leaf and ear groups showed strong antioxidant activities in the ABTS^??+ scavenging test. CONCLUSION The contents of the main constituents in Prunella vulgaris L stem leaf and ear have significance differences.The RESULTS of animal tests indicate that the aqueous extracts of Prunella vulgaris L stem leaf and ear have significant anti-inflammatory and antioxidant effects.     

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??OBJECTIVE To investigate the pharmacokinetics and bioequivalence of hyaluronic acid-graft-poly(ethylene glycol)/??-cyclodextrin nanocapsules loaded with asparaginase(AHAPs) in SD rats. METHODS Rats were randomly divided into two groups. After intravenous injecting AHAPs and free AN, the activity of AN in two groups was assayed at different time points. The pharmacokinetic parameters were calculated by software DAS2.1.1 and the bioequivalence of free AN and AHAPs was judged. RESULTS AUC_{0-48 h} of AHAPs and free AN were (132.26??1.59) and (46.38??1.98) U??h??mL^-1. MRT_{0-48 h} of AHAPs and free AN were (3.64??0.04) and (1.76??5.99) h. The t_max of AHAPs and free AN were (0.75??0) and (0.08??0) h, respectively. The results showed that AUC_{0-48 h}, MRT_{0-48 h} and t_max of AHAPs increased to 2.85, 2.07 and 9.37 times, respectively, as compared with free AN. The 90% confidential intervals of AUC_0-48h, AUC_0-?? and ??_max of tested formulation were 77.0%-78.5%, 77.0%-78.5%, 94.4%-96.0%, respectively. The t_max checked by nonparametric method has significant difference (P<0.05) between AHAPs and free AN. CONCLUSION AHAPs can improve the bioavailability and extend the action time of AN in rats. AHAPs and free AN were not bioequivalent. And AHAPs had better pharmacokinetics properties in rats.     

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??OBJECTIVE To prepare compound aspirin and esomeprazole magnesium enteric-coated pellet capsules and evaluate the drug release in vitro/in vivo. METHODS The aspirin pellet cores were prepared by using extrusion-spheronization method, and the esomeprazole magnesium-containing drug pellets were prepared with fluidized bed. By using fluidized bed coating method, the two kinds of drug-containing pellets were respectively coated with enteric layer to obtain enteric-coated pellets. After determining the loading capacity by measuring drug content, the two kinds of drug-containing pellets were filled into No.1 capsules. In vitro release was evaluated by measuring release percentage. The in vivo release behavior was evaluated by determination of pharmacokinetic parameters in rats. RESULTS The cumulative release percentage of the two drugs was less than 5% in 2 h in 0.1 mol??L^-1 hydrochloric acid solution. The cumulative release percentage of aspirin was more than 70% in 45 min in pH 6.8 PBS and it was more than 80% in 30 min for esomeprazole magnesium. Aspirin was metabolized to salicylic acid in plasma and its main pharmacokinetic parameters were as follows:t_1/2=9.47 h, MRT_0-??=14.43 h, t_max=3.00 h, ??_max=51.34 mg??L^-1, AUC _0-24=703.39 mg??h??L^-1, AUC _0-??=860.52 mg??h??L^-1. The pharmacokinetic parameters for esomeprazole magnesium were as follows:t_1/2=3.72 h, MRT_0-??=7.44 h, t_max=1.50 h, ??_max=2.71 mg??L^-1, AUC_0-24=11.89 mg??h??L^-1, AUC_0-??=13.79 mg??h??L^-1. CONCLUSION The formulation of compound enteric-coated pellet capsules is reasonable, and the preparation technology has good reproducibility. The drug release is located in the intestinal tract, thus esomeprazole magnesium can antagonize the gastrointestinal side effects of aspirin and aspirin can produce better antithrombotic effect .     

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??OBJECTIVE To study the pharmacokinetics of pirfenidone in Chinese healthy volunteer after a single dose and multiple-dose administration. METHODS Twelve Chinese healthy volunteers were randomly divided into low, medium and high dose groups(200, 400, 600 mg). The multiple-dose group was administrated with pirfenidione 400 mg three times daily for 5 d. Intensive blood sampling was performed from 12 volunteers within 12 h after the single dosing and the last dose of the multiple dosing. HPLC-MS/MS was used to determine the plasma concentrations of pirfenidone. The pharmacokinetic parameters were calculated by DAS software. RESULTS The main pharmacokinetic parameters of pirfenidone after single-dose administration of 200,400,600 mg qd as follows: ??_max were(5.00??1.42),(9.43??2.74)and(14.14??3.36)mg??L^-1;t_max were(0.57??0.33),(0.60 ??0.30)and(0.60??0.38)h;t_1/2 were(2.16??0.77),(2.15??0.75)and(2.01??0.76)h; AUC_0-?? were(13.87??7.79),(29.26??12.02)and(45.85??20.25)mg??h??L^-1;AUC_0-12 were?(13.27??7.08),(27.92??10.56)and(43.98??18.14)mg??h??L^-1,respectively. The main pharmacokinetic parameters after 400 mg tid for 5 d were as follows: ??_max was(9.46??2.77)mg??L^-1,??_min was(1.14??1.11)mg??L^-1,t_max was(0.52??0.34)h,t_1/2 was(1.93??0.63)h,AUC_0-?? was(26.74??13.49)mg??h??L^-1,AUC_0-12 was (25.79 ??12.34)mg??h??L^-1,AUC_sswas(23.53??10.59)mg??h??L^-1.CONCLUSION The pharmacokinetic parameters of pirfenidone show that ??_max and AUC were linear in the dose range from 200-600 mg and the pharmacokinetic parameters were similar as reference.
     

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??OBJECTIVE To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS Araloside A was administered in a dose of 50 mg??kg^-1 via gastric in fusion and 5 mg??kg^-1 by intravenous injection in rats.Araloside A was analyzed by a validated LC-MS/MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS The RESULTS of pharmacokinetic study showed that the linear range of araloside A was good in 1.0-10 000.0 ??g??L^-1(r>0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg??kg^-1 and intravenous injection of araloside A 5 mg??kg^-1 were as follows:t_1/2 was(8.65??3.22) and(2.00??0.21)h, AUC_0-t was(277.14??101.00) and (21 194.59??4 385.13)ng??h??L^-1, MRT_0-t was (7.88??0.64) and (1.21??0.11)h, Vd/F was (2 229.99??1 013.97) and (0.71??0.20)L??kg^-1, CL/F was(149.11??62.28) and (0.24??0.05) L??h^-1??kg^-1, respectively; ??_max was (32.68??10.74) ??g??L^-1 for intragastric administration and t_max reached(1.21??0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.     

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??OBJECTIVE To delevop a UPLC-MS method for determining the content of olein in rat plasma, and investigate the pharmacokinetics and bioavailability of nanoparticles of coix seed oil in rats. METHODS The rats were divided into three groups randomly. They were administered orally suspension of the raw material of the coix seed oil, Kang lai te soft capsules and nanoparticles of coix seed oil, respectively. Blood samples were collected at 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h and the concentrations of olein in rat plasma were determined by UPLC-MS. The pharmacokinetic parameters were calculated by 3P97 pharmacokinetic program. RESULTS The pharmacokinetic parameters of olein in the the raw material of coix seed oil, KLT soft capsules and nanoparticles of coix seed oil in rat plasma were as follows: ??_max were (5.43??0.45), (7.54??0.44) and (7.30??1.13) mg??L^-1, respectively, with significant difference between the nanoparticles and raw material (P<0.05), while no significant difference between nanoparticles and common oral prepatation(P>0.05); AUC_0-?? were (68.71??5.12), (46.61??3.86), and (178.91??6.26) mg??h??L^-1, respectively, which was the highest for the nanoparticles. The relative bioavailability of olein in the nanoparticles of coix seed oil was 260.38% to the raw material and 383.84% to the common oral prepatation. CONCLUSION The nanoparticles system can increase the bioavailability of coix seed oil and improve its biopharmaceutical property.     

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??OBJECTIVE To optimize vancomycin regimen in children with MRSA infection. METHODS Vancomycin AUC_0-24/MIC predictions were performed across a range of dosages (20-70 mg??kg^-1??d^-1) using a Monte Carlo simulation (n=10 000). AUC_0-24 was calculated as daily dose divided by vancomycin clearance, and daily dose was fixed for a given simulation. The MIC distribution for MRSA was obtained from the RESULTS of clinical laboratory, the First Affiliated Hospital of Guangxi Medical University, from 2012 to 2014 (n=430;30%??0.5 mg??L^-1; 58.6%= 12 mg??L^-1; and 11.2%=2 mg??L^-1; 0.2%=4 mg??L^-1). RESULTS With increasing vancomycin daily dose, the percentage of patients predicted to achieve AUC_0-24/MIC >400 similarly increased. At 35 mg??kg^-1??d^-1, the percentage predicted to achieve AUC_0-24/MIC >400 was 99.41% when MIC was 0.5 mg??L^-1. However, the dosage rose to 65 mg??kg^-1??d^-1 when MIC was 1 mg??L^-1. At this regimen, the percentage predicted to achieve AUC_0-24/MIC >400 was 97.55%. At a MIC of 2 mg??L^-1 and more, none of the dosages predicted to achieve AUC_0-24/MIC>400. CONCLUSION Recommended empiric vancomycin dosing in children should be above 35 mg??kg^-1??d^-1 when MIC is 0.5 mg??L^-1. At the MIC is 1 mg??L^-1, the recommended regimen should be over 65 mg??kg^-1??d^-1.     

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??OBJECTIVE To study the pharmacokinetics and bioequivalence of hydroxysafflor yellow A (HSYA) and hydroxysafflor yellow A nanoemulsion (HYAN) in rats.METHODS Twelve male rats were randomly divided into two groups. The rats were administered intragastrically with HSYA or HYAN, respectively, and then blood was collected from the venous plexus at different time points. HPLC method was used for the determination of HSYA blood concentration.RESULTS The main pharmacokinetic parameters of HYAN were as follows: the area under curve (AUC_{0-24 h}), peak concentration (??_max), peak time (t_max) and clearance (CL) were (31.56??4.58) mg??L??h^-1, (12.75??2.64) mg??L^-1, (0.83??0.54) h and (1.89??0.93) L??h^-1??kg^-1, respectively. The AUC_{0-24 h}, ??_max and t_max of HYAN increased by 5.49, 10.22 and 2.50 times, respectively, and the CL of HYAN was only 1/4 of that of HSYA. The 90% confidence intervals for AUC_{0-24 h} and ??_max were not within the prescribed range of bioequivalence criteria.CONCLUSION Relative to HSYA, the high plasma concentration and prolonged peak time of HYAN in vivo can significantly improve the oral bioavailability of HSYA. HSYA solution and HYAN are not bioequivalent.     

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??OBJECTIVE To investigate the influence of tripterygium glucoside tablet on the pharmacokinetics of atorvastatin in rats. METHODS Twelve rats were equally randomized to two groups (six rats in each group), including the atorvastatin-only group (A) and the tripterygium glucoside tablet and atorvastatin group (B). Animals in group A were administered according the oral dose of 2 mg??kg^-1; and animals in group B were administered at an oral dose of atorvastatin (2 mg??kg^-1)and tripterygium glucoside tablet (2 mg??kg^-1). Blood samples were collected into a heparinized tube via the oculi chorioideae vein at different time points after drug administration, and the plasma concentration of atorvastatin were determined using HPLC-UV. Finally, the pharmacokinetic profiles of atorvastatin were calculated and compared. RESULTS Compared with the atorvastatin-only group(A), the pharmacokinetic parameters of the tripterygium glucoside tablet and atorvastatin group(B) have changed greatly. ??_max of atorvastatin increased from (4.77??0.64) to (7.79??0.61) mg??L^-1, and AUC_0-t increased from (12.82?? 3.50) to (27.39??5.76) mg??h??L^-1, at the same time, t_max was extended from (0.25??0.03) to (0.52??0.07) h, t_1/2 was prolonged from (2.39??0.19) to (5.09??1.35) h, MRT was extended from (2.93??0.23) to (4.36??0.44)h. It indicates that the metabolism of atorvastatin may be suppressed. CONCLUSION The RESULTS indicate that tripterygium glucoside tablet could influence the pharmacokinetics of atorvastatin when atorvastatin and tripterygium glucoside tablet are used concomitantly. This study could be used for clinical medication guidance of tripterygium glucoside tablet and atorvastatin to avoid the occurrence of adverse reactions.     

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??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t_1/2 were (347.33??9.32) and (390.82??8.78) min, t_max were (30.00??5.94) and (60.00??3.48) min, ??_max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL^-1, AUC_0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL^-1, AUC_0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL^-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L^-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L^-1??min^-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t_1/2, lower ??_max and delayed t_max in rats.     

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??OBJECTIVE To characterize the metabolism of genistin and study its enzymatic kinetics in rat liver microsome by HPLC-MS. METHODS Genistin was incubated with rat liver microsomal incubation system. HPLC-MS method was used to characterize the metabolites. A metabolite generation method was established for quantitative analysis of genistein with sulfamethoxazole as internal standard.The enzyme kinetics parameters V_max and K_m was calculated by the GraphPad Prism 5.0 software. RESULTS The metabolites in vitro incubation system was identified as genistein.The optimal time in rat liver microsomes incubation time of 40 min,the optimal protein concentration of 1 mg??mL^-1,a substrate concentration of 50 ??mol??L^-1.The enzyme kinetics parameters of genistein were as follows: V_max=(0.104 2??0.003 3) ??mol??min^-1??mg(pro)^-1, K_m=(28.96??2.80) ??mol??L^-1. CONCLUSION The results indicate that genistin can be metabolited as the form of hydroxylation in rat liver microsome. Metabolite generation method is a reliable and simple method for determination of kinetic parameters of hepatic microsomal enzymes, and enzyme kinetic parameters obtained of genistin provide important parameters for further study.