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??OBJECTIVE To establish an UPLC-MS method for simultaneously determining the contents medical components of neohespiridin and naringin in rat plasma, meanwhile to investigate the pharmacokinetics for Daidai flavonoids lipid-lowering dropping pills and Daidai flavones extraction were compared in rats. METHODS We are established an UPLC-MS method to simultaneously determine the content of effective components(neohesperidin and naringin) of Daidai fruit flavones lipid-lowering dropping pills in rat plasma, measured blood drug concentration in rats, fitted medicine curve, analyzed and compared the pharmacokinetic process in vivo of Daidai fruit flavones lipid-lowering dropping pills and Daidai fruit flavonoids extracts, to evaluate the oral bioavailability improvement of Daidai fruit flavones lipid-lowering dropping pills. RESULTS The pharmacokinetics experimental results of rat gastric drug delivery with Daidai fruit flavonoids extract compared with that of rat with Daidai fruit flavones lipid-lowering dropping pills showed that the ??_max of neohesperidin in medicated serum is(1.68??0.02) _extract and(5.54??0.09) _{dropping pills}mg??L^-1, respectively; the ??_max of naringin is(1.50??0.05) _extract and(4.83??0.10) _{dropping pills}mg??L^-1, respectively; the ??_max and AUC_0~?? of Daidai fruit flavones lipid-lowering dropping pills were significantly higher than that of Daidai fruit flavonoids extraction(P<0.05), and MRT and t_1/2 of Daidai fruit flavones lipid-lowering dropping pills were significantly shorter than that of Daidai fruit flavonoids extracts.With Daidai fruit flavonoids extract as reference, the relative bioavailability of neohesperidin and naringin in dropping pills were 278.52% and 258.59%, respectively. CONCLUSION Daidai flavones dropping pill can significantly improve the medical components of neohespiridin and naringin oral bioavailability of Daidai flavones extraction.     

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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 study evodiamine complex nanoemulsion oil-in-water (EPBCN) in vitro and in vivo evaluation, about release in vitro and pharmacokinetics. METHODS Release in pH 1.2 hydrochloric acid and pH 6.8 PBS solutions and oral bioavailability in rats of EPBCN would be studied. The bioequivalence between evodiamine (ED) and EPBCN was judged. RESULTS In vitro release of EPBCN was about 2.61 times higher than that of ED. The oral bioavailability of EPBCN was 7.35 folds than that of ED. 90% confidence interval of area under concentration-time curve (AUC_{0-72 h}) and peak concentration (??_max) exceeded the standard range. CONCLUSION EPBCN can remarkably increase the release in vitro and oral bioavailability in rats, and they do not have bioequivalence.     

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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 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 investigate the pharmacokinetics of mycophenolate mofetil in patients with myasthenia gravis, and evaluate the correlation between plasma concentration and AUC. METHODS Eight myasthenia gravis patients older than 18 years old with normal liver and renal function were included in this study. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10 h after the patients were continuously given oral mycophenolate mofetil 2 g??d ^-1for one week. Plasma concentrations of mycophenolate mofetil were determined by HPLC method and data analysis was done by WinNonlin program. RESULTS The main pharmacokinetic parameters of mycophenolate mofetil were as follows??_max was (11.39??3.23) ??g??mL^-1,t_max was (1.5??0.8) h,AUC_{0-12 h} was (38.71??11.23) ??g??h??mL^-1. The ??₂ had the best correlation with AUC (r²=0.80) followed by ??₀ and ??₄ (r²=0.75). CONCLUSION The pharmacokinetics of mycophenolate mofetil has great inter-individual differences, but without significant difference with those in healthy volunteers and transplant patients. The ??₀ can be used for routine therapeutic drug monitoring because of convenience and feasibility.     

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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 evaluate the bioequivalence of tested and reference torasemide tablets in healthy male volunteers. METHODS A single oral dose of the two formulations was given to 24 healthy male volunteers according to a randomized crossover design. Plasma drug concentrations were determined by HPLC-MS. RESULTS The pharmacokinetic parameters of torasemide of the two preparations were as follows: ??_max (1 408.29??337.27) and (1 487.86??360.24) ng??mL^-1, t_max (0.90??0.42) and (1.03??0.50) h, t_1/2(4.43??0.57) and (4.43??0.60) h, MRT (3.90??0.60) and (4.01??0.72) h, AUC_{0-24 h}(3 886.86??865.99) and (3 906.06??761.72) ng??h??mL^-1, AUC_0-?? (3 936.57??903.93) and (3 956.96??789.98) ng??h??mL^-1, respectively. The relative bioavailability of tested torasemide tablets were (99.8??11.7)% and (99.7??12.0)% when calculated by AUC_{0-24 h} and AUC_0-??, respectively. CONCLUSION The two formulations of torasemide are bioequivalent in healthy Chinese volunteers.     

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??OBJECTIVE To prepare a nasal gel of risperidone (RIS) and evaluate its in vitro quality. METHODS The formulation and preparation process of RIS nasal gel were optimized with orthogonal test using appearance,spreading ability and in vitro release as main evaluation indexes. The quality items of the optimized RIS nasal gel such as appearance,pH value,contents of RIS and preservative,in vitro release and related substances were then evaluated. RESULTS The optimal formulation of the RIS nasal gel consisted of 0.5% RIS,0.35% carbopol 940,0.5% chlorobutanol,20% propanediol and 15% DM-??-CD and appropriate amount of purified water. Its ideal pH value was about 6.0. Furthermore,the quality items such as the appearance,pH value,contents of RIS and preservative,in vitro release and related substances of the preparation all conformed to the relevant quality requirements in China Pharmacopiea (2010). CONCLUSION The RIS nasal gel will be a promising new preparation for nasal administration due to its reasonable formulation,simple preparation process and controllable quality.     

石杉碱甲二元醇质体温敏凝胶大鼠鼻腔给药药动学及脑靶向性研究

目的 研究石杉碱甲二元醇质体温敏凝胶大鼠鼻腔给药药动学及脑靶向性.方法 UPLC-MS/MS法测定大鼠血浆及脑组织中石杉碱甲含量,计算主要药动学参数及脑靶向评价参数.结果 与温敏凝胶鼻腔给药及石杉碱甲注射剂静脉给药比较,二元醇质体温敏凝胶鼻腔给药大鼠脑组织AUC0～t升高(P<0.01),MRT0～t延长(P<0.05...