Publications (14)19.56 Total impact
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Article: Simple and Sensitive Determination of Metformin in Human Plasma Using an Ion-Pair LC Method
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ABSTRACT: A simple, selective and sensitive ion-pair liquid chromatography method was described for the determination of metformin in human plasma. Plasma samples (200μL) were deproteinated with 10% (v/v) perchloric acid followed by LC analysis using a Symmetry C18 column and a mobile phase of 29% acetonitrile—71% 2mM sodium dodecyl sulfate (with 350μL 0.1M HCl) operated at a flow rate of 1.5mLmin−1. Metformin and the internal standard (sodium phenytoin) were detected at 232nm and eluted at 6.8 and 7.9min, respectively. Calibration curves were linear (r>0.9990) between 9 and 2,000ngmL−1. The quantitation limit was 9ngmL−1, intra- and inter-day precision (CV) were 5.26% or less, and accuracy values were found to be within 5.95% of the nominal concentration.Chromatographia 04/2012; 70(9):1511-1514. · 1.20 Impact Factor -
Article: Genetic association of FOXP3 gene polymorphisms with allograft rejection in renal transplant patients.
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ABSTRACT: FOXP3 gene is known to be important for regulatory T cell development and function, and is associated with the rejection of human kidney transplants. The present study was therefore conducted to determine the effect of FOXP3 polymorphisms on allograft rejection in renal transplant recipients. A total of 166 adult patients were categorized into either a Rejection group (65 patients) or a No rejection group (101 patients). Rs3761547, rs3761548 and rs2232365 variant alleles in the FOXP3 gene were genotyped using a TaqMan probe technique, and their relationships with rejection were investigated. There was no significant difference in the genotype frequencies of rs3761547 and rs2232365 variants between patients with and without rejection history (P > 0.05). Binary logistic regression analysis showed that the rs3761548 AA genotype carriers were associated with about a fourfold greater risk for rejection compared with CC genotype (5 years post-transplant: odds ratio 3.95, 95% confidence interval 1.27-12.29, P = 0.018). Kaplan-Meier analysis revealed a lower mean time to the first rejection in rs3761548 AA compared with CC genotype patients (Log rank = 4.303, P = 0.038). Multivariate Cox regression analysis indicated that rs3761548 AA genotype carriers have up to about a twofold (hazard ratio 2.37, 95% confidence interval 1.17-4.80, P = 0.017) higher risk for rejection than CC carriers. Our study suggests an association between FOXP3 rs3761548 polymorphisms and allograft rejection in renal transplantation. This association should be further proven in large prospective studies because of the small sample size and confounding factors in this retrospective study.Nephrology 01/2012; 17(4):423-30. · 1.31 Impact Factor -
Article: Ginsenoside Rb1 inhibits proliferation and inflammatory responses in rat aortic smooth muscle cells.
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ABSTRACT: Ginsenoside Rb1, a known phytoestrogen, is a major pharmacologically active component in ginseng. The present study was designed to investigate the effect of ginsenoside Rb1 on fetal bovine serum (FBS)-induced proliferation and tumor necrosis factor-α (TNF-α)-evoked inflammatory responses in cultured rat aortic vascular smooth muscle cells (VSMCs). The data showed that Rb1 potently inhibited VSMC proliferation and cell growth induced by 5% FBS. These inhibitory effects were associated with G(1) cell cycle arrest and down-regulation of cell cycle proteins. Treatment with Rb1 reduced FBS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Furthermore, TNF-α-evoked inflammatory responses were inhibited by Rb1. Reporter gene assay indicated that Rb1 could transactivate ERβ especially. Moreover, Rb1-mediated inhibition of VSMCs proliferation was greatly blocked by transfection of ERβ siRNA. These results suggest that Rb1 inhibits FBS-induced proliferation and TNF-α-evoked inflammatory responses in VSMCs. The findings presented here highlight the possible therapeutic use of Rb1 in cardiovascular disease.Journal of Agricultural and Food Chemistry 06/2011; 59(11):6312-8. · 2.82 Impact Factor -
Article: Simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine in human plasma by high-performance liquid chromatography.
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ABSTRACT: A simple and sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method has been developed and validated for simultaneous quantification of five local anesthetics in human plasma: procaine, lidocaine, ropivacaine, tetracaine and bupivacaine. In an ice-water bath, 500 microL plasma sample, containing 100 microg/mL neostigmine methylsulfate as anticholinesterase, was spiked with carbamazepine as internal standard and alkalized by sodium hydroxide. Liquid-liquid extraction with ethyl ether was used for plasma sample preparation. The chromatographic separation was achieved on a Kromosil ODS C18 column with a mobile phase consisting of 30 mM potassium dihydrogen phosphate buffer (0.16% triethylamine, pH adjusted to 4.9 with phosphoric acid) and acetonitrile (63/37, v/v). The detection was performed simultaneously at wavelengths of 210 and 290 nm. The chromatographic analysis time was 13 min per sample. The calibration curves of all five analytes were linear between 0.05 and 5.0 microg/mL (r(2) > or = 0.998). Precision ranged from 1.4% to 7.9% and accuracy was between 91.7% and 106.5%. The validated method is applicable for simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine for therapeutic drug monitoring and pharmacokinetic study.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 03/2010; 878(15-16):1185-9. · 2.78 Impact Factor -
Article: Development of a liquid chromatography-isotope dilution mass spectrometry method for quantification of fentanyl in human plasma.
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ABSTRACT: Fentanyl is a potent analgesic drug in relieving chronic pain in patients. In this report, we present a simple, reliable and sensitive LC-ID/MS method for the quantification of fentanyl in human plasma. LC-ID/MS analysis was carried out on a triple quadrupole mass spectrometer operated in positive electrospray ionization multiple-reaction-monitoring using the transitions m/z 337.6 --> 187.9 for fentanyl and m/z 342.6 --> 187.9 for the internal standard (D5-fentanyl). The calibration curve covered the range 0.02-10 ng/mL. The intra- and inter-batch precision were less than 6.739 and 3.126% for fentanyl and IS, with accuracy from 94.16 to 102.0%. The lower limit of quantification was identifiable and reproducible at 0.02 ng/mL. The validated method offered increased sensitivity and wide linear concentration range. This method was successfully adopted for the evaluation of bioequivalence of two fentanyl transdermal preparations after single dose administration to 20 Chinese pain-patients.Biomedical Chromatography 11/2009; 24(7):711-6. · 1.97 Impact Factor -
Article: Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients.
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ABSTRACT: This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients. Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of cyclosporin dose reduction and cyclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with cyclosporin, sirolimus and corticosteroids during the first 3 months followed by either cyclosporin dose reduction or cyclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations (C(0)) from 112 patients were used to develop a population pharmacokinetic model using the NONMEM program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, cyclosporin daily dose, cyclosporin C(0) as well as other commonly used co-medications were explored. The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 10.1 l h(-1) (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or cyclosporin C(0). Moreover, CL/F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates from NONMEM. These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients.British Journal of Clinical Pharmacology 08/2009; 68(1):47-60. · 2.96 Impact Factor -
Article: [Development and identifiability analysis of parent-metabolite pharmacokinetic model for risperidone and its main active metabolite 9-hydroxyrisperidone].
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ABSTRACT: To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.Yao xue xue bao = Acta pharmaceutica Sinica 07/2007; 42(6):631-8. -
Article: [Simultaneous determination of the inhibitory potency of compounds on the activity of five cytochrome P-450 enzymes using a cocktail probe substrates method].
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ABSTRACT: This study developed a method for simultaneously assessing the inhibitory potency of compounds on five major cytochrome P-450 ( CYP450) enzymes using a cocktail of probe substrates. A cocktail selective substrates consisting of the phenacetin (PN, CYP1A2), dextromethorphan (DM, CYP2D6), tolbutamide (TB, CYP2C9), omeprazole (OPZ, CYP2C19) and midazolam (MPZ, CYP3A4) was incubated with human liver microsomes. The concentrations of the substrate metabolites paracetamol, dextrorphan, 4-hydroxytolbutamide, 5-hydroxyomeprazole and 1'-hydroxymidazolam were determined by LC/MS/MS in a single assay sample. The method was validated by incubating known CYP inhibitors--alpha-naphthoflavone (ANF, CYP1A2), quinidine (QND, CYP2D6), sulfaphenazole (SUL, CYP2C9), fluconazole (FLU, CYP2C19) and ketoconazole (KET, CYP3A4) with the individual substrates and with the substrate cocktail. The IC50 values were then determined. The IC50s (micromol x L(-1)) were in good agreement with those obtained with individual substrates (alpha-naphthoflavone, 0.18 vs 0.26; quinidine, 0.058 5 vs 0.058 4; sulfaphenazole, 0.48 vs 0.45; fluconazol, 17.5 vs 11.4; ketoconazole, 0.22 vs 0.24) and with previously reported values in the literature. This cocktail probe substrate method can be utilized for the rapid simultaneous determination of the inhibition potential of compounds on the five CYP450 enzymes.Yao xue xue bao = Acta pharmaceutica Sinica 07/2007; 42(6):589-94. -
Article: Isocratic Reversed-Phase HPLC for Simultaneous Separation and Determination of Seven Antiepileptic Drugs and Two of their Active Metabolites in Human Plasma
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ABSTRACT: A simple reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of the antiepileptic drugs (AEDs) zonisamide (ZNS), primidone (PRI), lamotrigine (LTG), phenobarbital (PB), phenytoin (PHT), oxcarbazepine (OXC), and carbamazepine (CBZ) and two of their active metabolites, monohydroxycarbamazepine (MHD) and carbamazepine 10,11-epoxide (CBZE) in human plasma. Plasma (100μL) was pretreated by deproteinization with 300μL methanol containing 20μgmL−1 propranolol hydrochloride as internal standard. HPLC was performed on a C8 column (4.6mm×250mm; particle size 5μm) with methanol–acetonitrile–0.1% trifluoroacetic acid, 235:120:645 (v/v), as mobile phase at a flow rate of 1.5mLmin−1. ZNS, OXC, and CBZ were monitored by UV detection at 235nm, and PRI, LTG, MHD, PB, PHT, and CBZE by UV detection at 215nm. Relationships between response and concentration were linear over the concentration ranges 1–80μgmL−1 for ZNS, 5–50μgmL−1 for PRI, 1–25μgmL−1 for LTG, 1–50μgmL−1 for MHD, 5–100μgmL−1 for PB, 1–10μgmL−1 for CBZE, 0.5–25μgmL−1 for OXC, 1–50μgmL−1 for PHT, and 1–25μgmL−1 for CBZ. Intra-day and inter-day reproducibility were adequate (coefficients of variation were ≤11.6%) and absolute recovery ranged from 95.2±6.13 to 107.7±7.76% for all the analytes; for the IS recovery was 98.69±1.12%. The method was proved to be accurate, reproducible, convenient, and suitable for therapeutic monitoring of the nine analytes.Chromatographia 02/2007; 65(5):267-275. · 1.20 Impact Factor -
Article: Total and free mycophenolic acid and its 7-O-glucuronide metabolite in Chinese adult renal transplant patients: pharmacokinetics and application of limited sampling strategies.
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ABSTRACT: This study aimed to investigate the pharmacokinetic characteristics of total and free mycophnolic acid (MPA) and its 7-O-glucuronide metabolite (MPAG) in Chinese renal transplant recipients. In addition, limited sampling strategies were developed to estimate the individual area under concentration curve (AUC) of total and free MPA. Total and free MPA and MPAG concentrations were determined by high performance liquid chromatography. Whole 12-h pharmacokinetic profiles were obtained on the 10th day after operation in 12 adult Chinese de novo renal transplant recipients administrated with mycophenolate mofetil (MMF, 750 mg bid), cyclosporine and corticosteroids. Limited sampling strategies with jackknife technique, a resampling method, and Bland-Altman analysis were employed to develop equations to estimate total and free MPA AUC. The pattern of total and free MPA and MPAG plasma concentration-time curves in the cohort of patients taking lower doses of MMF was consistent with previous reports of Caucasian patients taking MMF 1 g bid, except that dose-normalized exposure of total and free MPAG was much lower in the current study than in those of the Caucasians. The mean C (max) and AUC(0-12h) of total and free MPA were 9.4 +/- 3.4 mg/L, 20.2 +/- 6.5 mg x h/L and 0.4 +/- 0.4 mg/L, 0.7 +/- 0.5 mg x h/L, respectively, whereas mean C (max) and AUC(0-12h) of total and free MPAG were 97.3 +/- 32.6 mg/L, 656.0 +/- 148.0 mg.h/L and 29.9 +/- 8.5 mg/L, 222.0 +/- 58.1 mg x h/L respectively. The mean fractions of free MPA and MPAG were 3.5 +/- 2.0 and 34.6 +/- 8.0%, respectively. No determinant was identified to influence the pharmacokinetics of total and free MPA and MPAG or the free fraction of MPA and MPAG. The combinations of C (2h)-C (4h) and C (1h)-C (2h)-C (3h) were the best to estimate free and total MPA AUC(0-12h) respectively, whereas the combination of C (2h)-C (3h)-C (4h) and C (1h)-C (2h)-C (4h) was the best to estimate both simultaneously. This is the first time that the pharmacokinetics profile of total and free MPA and its main metabolite MPAG has been examined in Chinese adult renal transplant patients. The limited sampling strategies proposed to estimate individual free and total MPA AUC could be useful in optimizing patient care.European Journal of Clinical Pharmacology 02/2007; 63(1):27-37. · 2.85 Impact Factor -
Article: Modified population pharmacokinetic model for enterohepatic circulation of mycophenolic acid and its application in a bioequivalence study
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ABSTRACT: Aim To propose and evaluate a population pharmacokinetics model that describes multiple peaks due to enteroheapitc recirculation of mycophenolic acid (MPA) based on physiological consideration. Methods Pharmacokinetics data was obtained from a bioequivalence study. Twenty healthy male volunteers were enrolled in a single-dose, randomized, two-way crossover study designed to compare the bioavailability of 0.5 g dispersible tablets with 0.5 g capsules. A population compartment model incorporating input from the gallbladder, consistent with food intake, was developed to account for enterohepatic circulation. Nonlinear mixed effect model (NONMEM) was employed to estimate the population pharmacokinetic parameters and the associated inter-and intra-subject variability. The model was also applied in the assessment of the relative bioavailability for two formulations and the results were compared with conventional noncompartment analysis. Results The proposed model well defined the enterohepatic circulation of MPA. The typical population CL/F estimation was 9.93 L/h with inter-subject variation of 20% at the mean body weight of 67 kg. The relative residual error was 33.5% and the apparent distribution volume of central compartment was correlated with body weight. The amount of MPA recycled into body was estimated to be 33.1% of the total amount absorbed. Lag time in absorption for dispersible tablets and capsules were about 0.1 h and 0.2 h respectively. The relative bioavailability assessment by the proposed model indicated that two formulations are bioequivalent, which was in agreement with the noncompartment analysis. Conclusion Population approach allowed a formal assessment of the pharmacokinetics profile of the enterohepatic circulation. The proposed population pharmacokinetic model could be employed in the individualized immunosuppressive therapy.Asian Journal of Pharmacodynamics and Pharmacokinetics. 01/2007; 7(7):153-160. -
Article: [Bioequivalence assessment of pioglitazone hydrochloride oral preparation by limited sampling strategy].
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ABSTRACT: To develop limited sampling strategy (LSS) for estimation of C(max) and AUC(0-t) and assessing the bioequivalence of two pioglitazone hydrochloride (PGT) preparations. Healthy subjects (n = 20), enrolled in a bioequivalence study, were received 30 mg PGT po of reference or test formulation. The plasma concentration of PGT was determined by the validated HPLC method. A multiple linear regression analysis of the Cmax and AUC(0-t) against the PGT concentration for the reference formulation was carried out to develop LSS models to estimate these parameters. The models were internally validated by the Jackknife method and externally validated using simulated sets generated by Monte Carlo method. The best model was employed to assess bioequivalence of the two PGT formulations. The linear relationship between pharmacokinetics parameters and single concentration point was poor. Several models for these parameters estimation met the predefined criteria (r2 > 0.9). The Jackknife validation procedure revealed that LSS models based on two sampling times (C1, C2.5 and C1.5, C2.5 for C(max); C1.5, C9 and C2.5, C9 for AUC(0-t) predict accurately. Mean prediction errors (MPE) were less than 3%, and mean absolute prediction error (MAE) were less than 9%. The prediction error (PE) beyond 20% was less than 5% of total samples. Model external validation by Monte Carlo simulated data indicated that the most informative sampling combinations were C1.5, C2.5 for C(max), and C1.5, C9 for AUC(0-t), respectively. MPE and MAE of the proposed models were less than 5% , and 9% respectively. The PE beyond 20% was less than 5% of the total. Bioequivalence assessment of the two PGT formulations, based on the best LSS models, provided results similar to those obtained using all the observed concentration-time data points, and indicated that the two PGT formulations were bioequivalent. The LSS method for bioequivalence assessment of PGT formulations was established and proved to be applicable and accurate. Thus, it could be considered appropriate for PGT bioequivalence study with inexpensive cost of sampling acquisition and analysis. Key words: pioglitazone hydrochloride; limited sampling strategy; Monte Carlo simulation; bioequivalenceYao xue xue bao = Acta pharmaceutica Sinica 09/2006; 41(9):893-8. -
Article: [Effect of MDR1 polymorphic expression on oral disposition of cyclosporine A].
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ABSTRACT: To determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM). Twenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile. MDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population. The MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.Yao xue xue bao = Acta pharmaceutica Sinica 01/2005; 39(12):971-4. -
Article: Population pharmacokinetics of carbamazepine in Chinese epilepsy patients.
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ABSTRACT: To investigate the pharmacokinetic profile of carbamazepine (CBZ) in Chinese epilepsy patients. Serum samples through concentrations at steady state (n = 687) were collected prospectively from 585 patients during routine clinical care. Data were analyzed by the non-linear mixed-effect modeling (NONMEM) technique with a one-compartment model of first-order absorption and elimination. The important determinants of clearance (CL) were total body weight (TBW); dose; patient age over 65 years (E); and comedication with phenytoin (PHT), phenobarbital (PB), or valproic acid (VPA) when VPA daily dose was greater than 18 mg/kg. The final pharmacokinetic model for relative CL and apparent distribution volume (V) were: Equation A population pharmacokinetic model was proposed to estimate the individual CL for Chinese patients receiving CBZ in terms of patient's dose, TBW, and comedications to establish a priori dosage regimens.Therapeutic Drug Monitoring 07/2003; 25(3):279-86. · 2.49 Impact Factor
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2005–2012
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Fudan University
- • School of Pharmacy
- • Department of Clinical Pharmacy
Shanghai, Shanghai Shi, China
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