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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 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 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 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 population pharmacokinetics of vancomycin (VAN) in Chinese neonates by nonlinear mixes-effects modeling software (NONMEM). METHODS One hundred and fifty-four VAN serum trough data from 91 neonatal patients were retrospectively collected from Suzhou Hospital Affiliated to Nanjing Medical University. A one-compartment model with first order elimination was used to describe structure pharmacokinetic model, and physiological maturity model was employed to screen covariates. The stability and prediction of the final model were evaluated by Bootstrap and normalized prediction distribution error (NPDE). The final model was applied to evaluate the percentage of AUC_{0-24 h}/MIC ?? 400 in neonatal patients by Monte Carlo Simulation, who were stratified according to gestational weeks, age and serum creatinine. RESULTS The weight, postmenstrual age and serum creatinine were identified as the most significant covariate on clearance. Bootstrap and NPDE showed the satisfactory stability and prediction performance of the final model. Moreover, the final model indicated that 96% of neonates with low serum creatinine (15 ??mol??L^-1) were not getting AUC_{0-24 h}/MIC??400, according to the current guidelines. CONCLUSION The population pharmacokinetic model of vancomycin in neonates is established successfully and could provide basis for the individualized therapy in neonatal patients.     

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??OBJECTIVE To assess the impact of chrysin and naringenin on the pharmacokinetics (PK) of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats. METHODS Fifteen rats were randomized into 3 groups of equal size, and administered orally 30 mg??kg^-1 SQV with or without 40 mg??kg^-1 chrysin or naringenin. The PK of SQV was assessed using non-compartmental analysis and the plasma concentrations of three groups were determined by LC-MS/MS. RESULTS The PK parameters values of SQV, SQV+ naringenin, SQV+ chrysin are as follows:AUC_0-t,882.91,861.32,934.84 ng??h??mL^-1; AUC_0-??,903.97,865.90,947.92 ng??h??mL^-1; ??_max,177.72,89.8,130.72 ng??mL^-1; t_max,1,2,0.5 h;t_1/2,11.73,12.61,13.33 h; MRT_0-??,27.09,31.63,26.60 h; CL/F,21.65,21.45,20.62 mL??kg^-1??h^-1. CONCLUSION Double peak phenomenon is observed in the plasma SQV profiles. Our study demonstrates that chrysin and naringenin can not significantly affect the SQV oral bioavailability and SQV PK profiles in rats.     

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??OBJECTIVE To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC_{0-12 h} were(43.62??16.20) and(42.02??14.40)mg??h??L^-1(P>0.05);??_max were (17.85??11.32) and (13.96??5.11) mg??L^-1(P>0.05);t_max were (2.72??1.74) and(1.32??0.42)h(P<0.05); ??₀ were (1.63??1.18) and (1.66??0.93) mg??L^-1(P>0.05); ??₁₂ were(1.84??2.09) and (1.81??1.76) mg??L^-1(P>0.05); CL were (14.12??5.30) and (19.66??5.99) L??h^-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.     

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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 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.