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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 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 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 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 establish an LC-MS/MS method for the determination of levetiracetam to investigate the pharmacokinetics of levetiracetam extended-release tablets at fasted and fed states. METHODS The separation was achieved on a Waters Symmetry C₁₈ column (3.9 mm??150 mm,5 ??m) with mobile phase consisting of acetonitrile-5 mmol??L^-1 ammonium acetate and 0.3% formic acid aqueous solution (10/90, V/V). Two subjects were randomly assigned to receive single oral dose of levetiracetam extended-release tablets 1 000 mg after being fasted and fed by a randomized crossover design. The plasma concentrations of levetiracetam were measured by LC-MS/MS. RESULTS The calibration curve of levetiracetam in human plasma was linear over the concentration rang of 0.100 0-80.00 ??g??mL^-1. Under fasted and fed conditions, the main pharmacokinetic parameters of levetiracetam were as follows:??_max were 20.50 and 19.09 ??g??mL^-1, AUC_{0-48 h} were 345.4 and 336.3 ??g??h??mL^-1, t_max were 4.5 and 7.0 h, respectively. CONCLUSION The method is proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetic study of 1 000 mg levetiracetam extended-release tablets in healthy Chinese volunteers after being fasted and fed. The result suggests that high fat and calories diet has effect on the pharmacokinetics of levetiracetam extended-release tablets, with t_max being delayed.     

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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 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 establish an HPLC-UV method for the simultaneous determination of valsartan and nifedipine in rats plasma, so as to study the pharmacokinetic interaction between valsartan and nifedipine and to provide useful information for clinical practice. METHODS Eighteen male Wistar rats were divided into three groups: valsartan group(16 mg??kg^-1), nifedipine group (4.2 mg??kg^-1) and combined group (containing valsartan 16 mg??kg^-1, nifedipine 4.2 mg??kg^-1). Plasma samples were collected at 0, 0.08, 0.16, 0.25, 0.5, 0.75, 1, 2, 4, 8, 10, 24 h after the drug administration. An HPLC with UV detection method was developed to determine the concentration of valsartan and nifedipine in rat plasma, and the pharmacokinetic parameters were calculated using non-compartment model. RESULTS Compared with single valsartan group, the pharmacokinetic parameters ??_max and AUC_0-t of the combined group had a significant increase(P<0.05), while Tmax and CLz/F had a significant decrease(P<0.05). Compared with single nifedipine group, the pharmacokinetic parameters t_1/2z/h had a significant decrease(P<0.05), while other pharmacokinetic parameters had no significant differences. CONCLUSION Combination of valsartan and nifedipine could significantly improve the valsartan in rats plasma concentration and bioavailability, increase absorption and decrease excretion , while nifedipine shows no pharmacokinetic change in rats except shortened half-life.