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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 evaluate the bioequivalence of cefdinir suspension and reference cefdinir capsule in Chinese healthy male subjects.METHODS A single oral dose of 100 mg cefdinir suspension or cefdinir capsule was given to 24 subjects according to a 2-way crossover design. The plasma concentrations of cefdinir were determined by UPLC-MS/MS. The pharmacokinetic parameters were calculated and bioequivalence was compared by WinNonlin 6.3 program. RESULTS The main pharmacokinetic parameters of cefdinir suspension and cefdinir capsule were as follow: ??_max were (1 034.78??358.17), (969.71??297.38) ng??mL^-1;t_max were (2.98??0.60), (3.44??0.70) h; AUC_0-12 were (4 911.24??1 675.30), (4 522.35??1 600.13) ng??h??mL^-1; AUC_0-?? were (5 026.24??1 735.32),(4 680.69??1 699.93) ng??h??mL^-1;t_1/2 were (1.71??0.23), (1.79??0.39) h. The 90% confidential interval of ??_max, AUC_0-12, AUC_0-?? of tested formulation were 95.6%-115.3%, 99.9%-117.2%, 99.0%-116.0%. CONCLUSION The two formulations are bioequivalent.     

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??OBJECTIVE To investigate the pharmacokinetics of matrine injection by different routes of administration. METHODS Twenty healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intraperitoneal and intravenous administration of matrine injection at dose of 15 mg??kg^-1 respectively. Blood samples (0.3-0.4 mL) were immediately collected into heparinized tubes before injection and at 0.033, 0.083, 0.167, 0.333, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters including AUC_0-12, AUC_0-??, MRT_0-12, MRT_0-??, t_1/2, Vd, CL and ??_max were calculated. RESULTS The main pharmacokinetic parameters for matrine after intraperitoneal and intravenous administration at dose of 15 mg??kg^-1 were as follows:AUC_0-12 (10 166??2 426), (12 217??2 968) ng??mL^-1??h;AUC_0-?? (10 230??2 432), (12 300??3 031)- ng??mL^-1??h;MRT_0-12 (1.91??0.41), (2.14??0.54) h;MRT_0-?? (2.01??0.41), (2.26??0.64) h; t_1/2(2.26??0.89), (2.60??1.25) h;Vd(4 998??2 010), (6 175??2 540) mL;CL (1 531??315.0), (1 727??475.6) mL??h^-1??kg^-1; ??_max (5 246??1 187), (8 503??1 101) ng??mL^-1, respectively. The bioavailability of intraperitoneal administration is 83.21%. CONCLUSION No significant differences were observed in AUC, MRT, t_1/2 and CL values of matrine between different administrations except for ??_max and Vd.     

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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 investigate the effect of high-fat and high-calorie diets on pharmacokinetics of cefuroxime axetil in healthy Chinese subjects. METHODS A randomized, open-label, single dose and two-way crossover clinical study was conducted. Twelve healthy subjects were randomly divided into two groups, each of which includes six males, then they were given 250 mg of cefuroxime axetil respectively before and after meal. Blood samples were collected at different time points before and after drug administration. The concentration of cefuroxime in plasma was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS3.2.8 and were analyzed by DAS3.2.8 and SPSS19.0. RESULTS The main pharmacokinetic parameters of fasting and postprandial were as follows: AUC_0-t was (11 402.8??3 556.7) and (18 565.7??2 917.9) ng??h??mL^-1, AUC_0-?? was (11 492.5??3 581.8) and (18 754.7??2 885.6) ng??h??mL^-1, ??_max was (3 406.7??1 188.9) and (5 439.2??1 118.2) ng??mL^-1, t_max was (2.01??0.64) and (2.08??0.79) h, t_1/2 was (1.66??0.38) and (1.60??0.60) h, respectively. The main pharmacokinetic parameters between fasting and high-fat meal groups were analyzed by SPSS19.0 software. There was significant difference in AUC_0-t, AUC_0-?? and ??_max(P<0.01), and no significant difference in t_max and t_1/2 (P>0.05). The ??_max and AUC were increased by 59.7% and 63.2% respectively, t_max is almost unchanged. The equivalence analysis was performed with DAS.3.2.8 software, the 90% confidence intervals for the ratios of AUC_0-t, AUC_0-?? and ??_max for the postprandial/fasting were 137.6%-217.5%, 138.4%-217.3%, 135.4%-207.6%, respectively. None of them fall within the acceptable interval of 80%-125%. CONCLUSION High-fat and high-calorie diets can significantly improve the extent of absorption of cefuroxime axetil in vivo, but does not affect the absorption rate of cefuroxime axetil.     

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??OBJECTIVE To develop an UPLC method for the determination of mycophenolic acid(MPA) for studying the pharmacokinetics of mycophenolate mofetil(MMF) dispersible tablets after multiple oral doses in early kidney transplant recipients for the rational use in the clinical practice.METHODS A total of 15 Chinese postoperative renal transplant recipients were given a multiple-dose of MMF (750 mg, q12 h) for 6 d. Their blood specimens (2 mL) were collected at 0 and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after drug oral administration on day 7. The concentrations of MPA in plasma were determined using UPLC-UV. The main pharmacokinetic parameters were assessed.RESULTS Determination of MPA had good linearity in the concentration range of 0.1-40 ??g??mL^-1, lower limit of quantization was 0.10 ??g??mL^-1.The main pharmacokinetic parameters on day 7 of MMF dispersible tablets were as follows:AUC_{0-12 h} was (24.63??9.51) ??g??h??mL^-1, ??_max was (6.51??3.27) ??g??mL^-1, t_max was (1.83??1.30) h, ??₀ was (1.26??0.99) ??g??mL^-1,CL was (34.66??12.45) L??h^-1. Most of the patients revealed a second small peak in the 4-12 h.CONCLUSION This established method is simple, rapid and suitable for determination of MPA in human plasma.Interindividual variability in AUC_{0-12 h}, ??_max and ??₀ values was considerable in the early renal transplant patients. The MPA exposures under the fixed dose of MMF are low. It is necessary to monitor the MPA-AUC_{0-12 h} to guide the adjustment of drug dosage.     

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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 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 evaluate the pharmacokinetics characteristics and safety of antipsytrotic ziprasidone mesylate with single dose intramuscularly injected in healthy volunteers. METHODS A total of 12 healthy Chinese volunteers(male 6 cases and female 6 cases) were received intramuscularly single dose of ziprasidone mesylate, the dosage was 10 mg.Blood samples were collected at different time after intramuscularly injection.The concentrations of ziprasidone in serum were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated. RESULTS The concentration-time curves of ziprasidone fitted to two-compartment model.The pharmacokinetic parameters were stated as follows, ??_max was (97.85?? 29.24) ng??mL^-1;t_max was (0.56??0.30)h;MRT was (5.35??0.96) h; t_1/2 was (4.29??0.88)h; AUC_0??t was (405.6??98.68) ng??h??mL^-1,AUC_0???? was (413.3?? 100.69)ng??h??mL^-1; CL was (25.50??6.10)L??h^-1; Vd was (157.48??47.60)L; Kel was (0.168??0.035)h. There were no significant differences of the parameters between the male and female subjects. The common adverse events were somnolence, nausea and weakness with the severity of mild to moderate. CONCLUSION The pharmacokinetic parameters in 12 healthy volunteers after intramuscular injection of 10 mg ziprasidone mesylate are in line with that reported in the literature. This medicine has effect of sedation, so that it could be used to control the excited agitation.     

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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.