Xiao-Jin Shi

Simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine in human plasma by high-performance liquid chromatography

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.

Association of ABCB1, CYP3A4*18B and CYP3A5*3 genotypes with the pharmacokinetics of tacrolimus in healthy Chinese subjects: a population pharmacokinetic analysis

What is known and Objective:  Tacrolimus (TAC) is metabolized mainly by the CYP3A subfamily and extruded into the intestine by P‐glycoprotein, which is encoded by the ABCB1 gene. Several studies have suggested that the CYP3A5*3 genotype influenced the pharmacokinetics (PK) of TAC. The CYP3A4*18B and CYP3A5*3 alleles are clinically important in Chinese subjects because of their relatively high frequency. The present study aimed at evaluating the effects of ABCB1 (C1236T‐G2677T/A‐C3435T), CYP3A4*18B and CYP3A5*3 genetic polymorphisms on TAC PK in healthy Chinese subjects.

Ginsenoside Rb1 inhibits proliferation and inflammatory responses in rat aortic smooth muscle cells.

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.

Population pharmacokinetics of carbamazepine in Chinese epilepsy patients.

Aim To investigate the pharmacokinetic profile of carbamazepine (CBZ) in Chinese epilepsy patients. Materials and Methods 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. Results 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:MATH Conclusion A population pharmacokinetic model was proposed to estimate the individual CL for Chinese patients receiving CBZ in terms of patients dose, TBW, and comedications to establish a priori dosage regimens.

Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data.

Objective:  To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine‐10,11‐epoxide (CBZE) in Chinese population.

Determination of berberine, palmatine and jatrorrhizine in rabbit plasma by liquid chromatography–electrospray ionization-mass spectrometry

Incurred rabbit plasmas samples were utilized for method quality assessment in this study, where an optimized protein precipitation method for the preparation of rabbit plasma samples and a rapid and sensitive liquid chromatography-electrospray ionization-mass spectrometry for the simultaneous determination of berberine, palmatine and jatrorrhizine was described. Plasma samples (100 μl) were pretreated by protein precipitation with the mixture of 3% formic acid and 50 ng/ml clozapine (internal standard) in acetonitrile followed by LC analysis using a C(18) column and a mobile phase composed of 0.4% formic acid solution and 0.2% formic acid solution of methanol (60:40, v/v) operated at a flow rate of 0.4 ml/min. The analysis was performed in the multiple reaction monitoring mode via electrospray ionization source operating in the positive ionization mode. The method was linear over the concentration range of 0.1-400 ng/ml for all target components. The lower limits of quantification were 0.1 ng/ml for all analytes, all intra- and inter-day precision values were less than 7.10%, and accuracy (bias, %) was within ±7.11%. The mean absolute recovery was more than 72% for all analytes. The validated method has been successfully applied to the pharmacokinetic study of berberine, palmatine and jatrorrhizine in rabbit plasma after oral administration of San-Huang decoction to rabbits.

6-Hydroxydaidzein enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells.

Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARγ) gene expression and PPARγ transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPα) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPα and facilitating the translocation of GLUT4 via the activation of PPARγ, suggesting that 6-HD can be promising in diabetes management.

Pharmacokinetic comparisons of berberine and palmatine in normal and metabolic syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE San-Huang formula is a popular traditional Chinese medicine (TCM) preparation to replenish Qi, resolve phlegm, dissipate blood stasis, and therapy metabolic syndrome in China. Metabolic syndrome, which is accompanied by Qi and blood stasis, mainly arises from spleen deficiency in essence. There is limited information available for differences of pharmacokinetic properties of San-Huang formula between normal and metabolic syndrome rats. The present study was conducted to compare the pharmacokinetics of berberine as well as palmatine in normal and metabolic syndrome rats following oral administration of San-Huang formula extract. MATERIALS AND METHODS The animals were orally administered with San-Huang formula extract with the equivalent dose of 60.4 and 12.5mg/kg for berberine and palmatine, respectively. The blood samples were collected according to the time schedule. The concentrations of berberine and palmatine in rat plasma were determined by LC-ESI/MS. Various pharmacokinetic parameters were estimated from the plasma concentration versus time data using non-compartmental methods. RESULTS It was found that AUC0-t, Cmax, Vd and CL of berberine and palmatine in metabolic syndrome rats were significantly different (P<0.05) from normal rats. CONCLUSIONS The results indicated that berberine and palmatine have higher uptake and slower elimination in the rats with metabolic syndrome, which suggests that the rate and extent of drug metabolism were altered in metabolic syndrome rats.

Anionic LPD complexes for gene delivery to macrophage: Preparation, characterization and transfection in vitro

In the present study, anionic lipid/peptide/DNA (LPD) complexes consisting of pH-sensitive liposome and protamine were introduced as the carriers targeting RAW 264.7 cell line, which had been reported to be difficult for transfection. The LPD complexes were physically characterized. The pH sensitivities and sizes of liposomes were investigated. The zeta potentials of LPD complexes altered significantly with the addition of protamine sulfate and anionic liposomes. It was demonstrated that the carriers produced an increase in the stability of plasmid DNA against DNase I. The TEM showed that the size distribution of LPD complexes was irregular. In the in vitro transfection, the efficiency of LPD complexes was higher than that of Lipofectamine™ 2000 and protamine/DNA complexes, but lower than that of electroporation. A possible mechanism for the internalization of plasmid DNA mediated by the anionic LPD complexes was also proposed. With a high safety certificated by MTT assay, LPD complexes prepared in this study might be potentially employed as a macrophage gene therapy.

Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients

AIMS 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. METHODS 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. RESULTS 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. CONCLUSIONS These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients.