Biomedical subjects

Zhonggui He

Publications and source records attributed to Zhonggui He.

15 recordsLinked to original sources

PubMed2006

Quantitative structure-retention relationship studies with immobilized artificial membrane chromatography II: partial least squares regression.

We aimed to establish quantitative structure-retention relationship (QSRR) with immobilized artificial membrane (IAM) chromatography using easily understood and obtained physicochemical molecular descriptors and to elucidate which descriptors are critical to affect the interaction process between solutes and immobilized phospholipid membranes. The retention indices (logk(IAM)) of 55 structurally diverse drugs were determined on an immobilized artificial membrane column (IAM.PC.DD2) directly or obtained by extrapolation method for highly hydrophobic compounds. Ten simple physicochemical property descriptors (clogP, rings, rotatory bond, hydro-bond counting, etc.) of these drugs were collected and used to establish QSRR and predict the retention data by partial least squares regression (PLSR). Five descriptors, clogP, rotatory bond (RotB), rings, molecular weight (MW) and total surface area (TSA), were reserved by using the Variable Importance for Projection (VIP) values as criterion to build the final PLSR model. An external test set was employed to verify the QSRR based on the training set with the five variables, and QSRR by PLSR exhibited a satisfying predictive ability with R(p)=0.902 and RMSE(p)=0.400. Comparison of coefficients of centered and scaled variables by PLSR demonstrated that, for the descriptors studied, clogP and TSA have the most significant positive effect but the rotatable bond has significant negative effect on drug IAM chromatographic retention.

Chromatography, High Pressure Liquid↗

PubMed2006

Quantitative structure-retention relationship studies using immobilized artificial membrane chromatography I: amended linear solvation energy relationships with the introduction of a molecular electronic factor.

Linear solvation energy relationships (LSERs) amended by the introduction of a molecular electronic factor were employed to establish quantitative structure-retention relationships using immobilized artificial membrane (IAM) chromatography, in particular ionizable solutes. The chromatographic indices, log k(IAM), were determined by HPLC on an IAM.PC.DD2 column for 53 structurally diverse compounds, including neutral, acidic and basic compounds. Unlike neutral compounds, the IAM chromatographic retention of ionizable compounds was affected by their molecular charge state. When the mean net charge per molecule (delta) was introduced into the amended LSER as the sixth variable, the LSER regression coefficient was significantly improved for the test set including ionizable solutes. The delta coefficients of acidic and basic compounds were quite different indicating that the molecular electronic factor had a markedly different impact on the retention of acidic and basic compounds on IAM column. Ionization of acidic compounds containing a carboxylic group tended to impair their retention on IAM, while the ionization of basic compounds did not have such a marked effect. In addition, the extra-interaction with the polar head of phospholipids might cause a certain change in the retention of basic compounds. A comparison of calculated and experimental retention indices suggested that the semi-empirical LSER amended by the addition of a molecular electronic factor was able to reproduce adequately the experimental retention factors of the structurally diverse solutes investigated.

Algorithms↗

PubMed2006

Distribution characteristics of orally administered olamufloxacin, a newly synthesized fluoroquinolone antibacterial, in lung epithelial lining fluid and alveolar macrophage in rats.

This study described distribution characteristics of olamufloxacin (HSR-903) in lung epithelial lining fluid (ELF) and alveolar macrophage (AM) in rats, two important representative infectious sites in lower respiratory tract infections. The rats were orally administered at a dose of 10mg/kg. At each designated time, rats were sacrificed, and blood samples were collected from the superior vena cava, and ELF and AM samples were gathered by the bronchoalveolar lavage method. The AUC ratios of ELF/plasma and AM/plasma of HSR-903 were 3.03+/-0.54 and 97.5+/-24.2, respectively, notably higher than those of ciprofloxacin (CPFX). Kinetic analyses of concentration-time profiles of HSR-903 in ELF and AM indicated that the influx clearance from plasma to ELF across the alveolar barrier was 5.8-fold higher than the efflux clearance from ELF. Furthermore, the permeability of HSR-903 across the cultured AM plasma membrane was 5.5 and 14.5 times greater than those of CPFX and pipemidic acid (PPA), respectively. A significant correlation (r2 = 0.995) was achieved between permeability across AM plasma membrane and hydrophobicity, implying that passage through AM membrane was principally involved in the passive diffusion. The extent of AM intracellular binding was the greatest for grepafloxacin, followed by HSR-903, CPFX, levofloxacin and PPA. In conclusion, HSR-903 distributed more efficiently in ELF and AM than CPFX, and the high accumulation of HSR-903 by AM cells may be accounted for by both the high transferability across the AM membrane and avid binding to the membrane phospholipids.

Administration, Oral↗

PubMed2006

Single and multiple dose bioequivalence evaluation of two brands of gliclazide modified release tablets in healthy Chinese male volunteers.

Randomized, two-way, crossover, single- and multiple-dose studies were conducted in healthy Chinese male volunteers to evaluate the bioequivalence of two brands of gliclazide (CAS 21187-98-4, 1-(3-azabicylco(3, 3, 0)oct-3-yl)-3-p-tolysulfonylurea) 30 mg tablets, viz. Gliclazide modified release (MR) tablets as test (T) and a commercial gliclazide standard preparation as reference (R) product. Each volunteer received T and R tablets separated by 7 days of a drug-free washout period. The plasma concentrations of gliclazide, determined by a validated LC-ESI-MS method, were employed to assess the pharmacokinetic parameters such as maximum and minimum observed plasma concentration (Cmax and Cmin), time to Cmax (tmax), average plasma concentration at steady state (Cav), area under plasma concentration curve (AUC(0-72), AUC(0-infinity) and AUC(ss), and degree of fluctuation for plasma concentration (DF %). As to these parameters, the analysis of variance (ANOVA) showed no significant difference and 90 % confidence intervals (CI) fell entirely into the acceptable range of bioequivalence. Based on these statistical inferences, the two formulations are considered bioequivalent in the extent and rate of absorption from both single- and multiple-dose studies.

Adult↗

PubMed2006

[Determination of contents and dissolution of ethambutol hydrochloride in fixed dose combinations for antituberculosis drugs by high performance liquid chromatography with pre-column derivatization].

A reversed-phase high performance liquid chromatographic method (RP-HPLC) with pre-column derivatization and ultraviolet (UV) detection was established to determine ethambutol hydrochloride in fixed dose combinations (FDCs) for anti-tuberculosis drugs. The derivatization was carried out in a non-aqueous environment, where ethambutol hydrochloride was derivatized with phenylethylisocyanate at an optimal molar ratio of 1:6. The extraction recovery was 98.7% with the mean relative standard deviation of 0.70%. The accuracy and precision of the method were all qualified. The linear regression of the standard calibration curve was determined and the linearity was good (r = 0.9993). The method is sensitive, specific, rapid, and can be successfully applied to the quantitation and dissolution of ethambutol hydrochloride in FDCs.

Antitubercular Agents↗

PubMed2006

A rapid HPLC/ESI-MS method for the quantitative determination of oridonin in rat plasma.

A rapid and accurate method using liquid chromatography with electrospray ionization mass spectrometric detection (HPLC/ESI-MS) was developed and validated for the determination of oridonin in rat plasma. The analytes were extracted with ethyl acetate-n-butyl alcohol (100:2, v/v) after spiking the samples with ethyl hydroxybenzoate (internal standard). The separation was carried out on a Diamon-sil C18 column with an isocratic mobile phase consisting of methanol-water (80:20, v/v) at a flow rate of 1.0 ml/min. The lower limit of quantification (LLOQ) of the method was 10 ng/ml and the linear range was 10-4000 ng/ml. The intra-day and inter-day accuracy and precision of the assay were less than 9%. This method has been applied successfully to a preliminary pharmacokinetic study involving the intravenous administration of oridonin to rats.

Animals↗

PubMed2005

Impact of pharmaceutical dosage forms on the pharmacokinetics of roxithromycin in healthy human volunteers.

OBJECTIVES: The impact of two different pharmaceutical preparations on the pharmacokinetics of roxithromycin was investigated in healthy human volunteers. METHODS: The degradation kinetics and products of roxithromycin were investigated in simulated gastric fluid and simulated intestinal fluid. Two oral dosage forms of roxithromycin were employed: enteric-coated pellets and dispersible tablets. RESULTS: The degradation half-time of roxithromycin in simulated gastric fluid was 0.23 h, and three main degradation products were characterized. In contrast, roxithromycin was stable in simulated intestinal fluid and remained unchanged after a 1.00 h incubation. The roxithromycin enteric-coated pellets exhibited higher bioavailability and a more potent serum antibacterial activity than the dispersible tablets. CONCLUSIONS: The type of oral dosage forms of roxithromycin altered its pharmacokinetics. Whether or not this affects the in vivo antibacterial efficacy requires further study.

Adult↗

PubMed2005

Study on the bioavailability of puerarin from Pueraria lobata isoflavone self-microemulsifying drug-delivery systems and tablets in rabbits by liquid chromatography-mass spectrometry.

To evaluate the bioavailability of puerarin from Pueraria lobata isoflavone self-microemulsifying drug delivery systems (SMEDDS) and Yufengningxin tablets, a rapid and specific liquid chromatography--mass spectrometric method was developed and validated to determine puerarin in rabbit serum. The analyte was extracted from serum samples by precipitating the serum proteins, separated on a Diamonsil C(18) column and detected by mass spectrometry with an electrospray ionization interface. 4-Hydroxybenzaldehyde was used as the internal standard. The method has a limit of quantitation of 10 ng/mL using 200 microL serum. The intra-day relative standard deviations (RSDs) ranged from 3.7 to 6.9% and inter-day RSDs were within 6.5%. After administration of SMEDDS and tablets to rabbits, a significant difference was observed in main pharmacokinetic parameters of t(max), C(max) and AUC(0--infinity) between SMEDDS and tablets, and a 2.2-fold increase in the relative bioavailability of puerarin was observed with the SMEDDS compared with Yufengningxin tablets. It was concluded that the absorption of puerarin from Pueraria lobata isoflavone SMEDDS was enhanced.

Administration, Oral↗

PubMed2005

Self-microemulsifying drug delivery systems (SMEDDS) for improving in vitro dissolution and oral absorption of Pueraria lobata isoflavone.

The aim of our investigation was to develop and characterize self-microemulsifying drug delivery systems (SMEDDS) of Pueraria lobata isoflavone to improve its in vitro dissolution and oral absorption in beagle dogs. SMEDDS consisted of oil (ethyl oleate), a surfactant (Tween 80), and a cosurfactant (Transcutol P). In all the SMEDDS, the level of Pueraria lobata isoflavone was fixed at 20% w/w of the vehicle. The in vitro self-microemulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. A pseudoternary phase diagram was constructed identifying the efficient self-microemulsification region. From these investigations, an optimized formulation was selected and its dissolution and bioavailability were compared with a tablet formulation in beagle dogs. The in vitro dissolution rate of puerarin from SMEDDS was more than threefold faster than that from Yufengningxin tablets (Pueraria lobata isoflavone tablets). A 2.5-fold increase in the relative bioavailability was observed for the SMEDDS compared with Yufengningxin tablets. The absolute bioavailability of the SMEDDS was 82.32 +/- 15.51%, which was significantly improved compared with that of Yufengningxin tablets. These results demonstrate the potential of SMEDDS as an efficient way of improving the oral absorption of Pueraria lobata isoflavone.

Administration, Oral↗

PubMed2005

[Immobilized artificial membrane chromatography and its application in profiling the drug membrane transport].

Immobilized artificial membrane chromatography (IAMC) is a system of covalently bonding monolayer of phospholipid analogs onto the solid surface of silica particles, thus establishing the emulating process of drug-cellular membrane interactions in terms of chromatographic method, and is applied to profile the drug membrane permeability and biological activity. IAMC phases prepared from phosphocholine analogues closely mimic the surface of the biological cell membrane, and the capacity factor of drugs can be used to predict the interaction between drug molecules and cell membranes. IAMC, compared with n-octanol/water, liposome/water and ODS chromatography, can simulate other forces besides hydrophobic interaction. IAMC is getting more and more profound research because of its convenience and high efficiency. The primary screening by means of IAMC in the early stage of drug development would effectively lower failure in the preclinical and clinical development, since efficacy and safety are related in the larger part to membrane permeability. The interaction mechanism of drug-IAM and its profiling in membrane transport are reviewed.

Chromatography↗

PubMed2005

Rapid and sensitive determination of indapamide in human blood by liquid chromatography with electrospray ionization mass spectrometric detection: application to a bioequivalence study.

A rapid and sensitive method using liquid chromatography with electrospray ionization mass spectrometric detection was developed and validated for the determination of indapamide in human blood. Blood samples were extracted with n-hexane-dichloromethane (1:1, v/v) and separation was performed on a Symmetry C18 column (150 x 3.9 mm i.d., 5 microm) with the mobile phase consisting of acetonitrile-water (60:40, v/v). Indapamide and internal standard (propylparaben) were detected by negative electrospray ionization and selected ion recording (SIR) at m/z 364 for indapamide and m/z 179 for propylparaben. This method has a lower limit of quantification (LLOQ) 2.0 microg/L with a linear calibration range of 2.0 microg/L to 120 microg/L. The method showed excellent reproducibility with an inter- and intra-assay precision of < 9.4% (% RSD), as well as excellent accuracy with an inter- and intra-assay accuracy of between 98.0 and 102%. Furthermore, the method was successfully applied to a bioequivalence study in which 20 healthy volunteers received a single oral dose of 3 mg reference and test sustained-release indapamide formulations, in an open, two-period, randomized crossover protocol. The maximum blood concentrations (C(max)) were 60.3 +/- 22.6 microg/L and 57.6 +/- 18.7 microg/L at 13.1 +/- 6.9 h and 18.3 +/- 7.4 h, the times to reach the peak concentration (T(max)), for the test and reference tablets, respectively. The relative bioavailability of the test tablets was 110.1 +/- 34.5%, compared with the reference tablets. There were no statistically significant differences in the main pharmacokinetic parameters, and the two formulations were judged to be bioequivalent.

Antihypertensive Agents↗

PubMed2004

Study on the bioavailability of nateglinide-hydroxypropyl-beta-cyclodextrin complex capsule in rabbits by liquid chromatographic-tandem mass spectrometry.

To evaluate the bioavailability of nateglinide-hydroxypropyl-beta-cyclodextrin (HPCD) complex, a rapid and specific liquid chromatographic-tandem mass spectrometric method was developed and validated to determine nateglinide in rabbit serum. The analyte was extracted from serum samples by liquid-liquid extraction, separated on a Zorbax C(18) column and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface. Daidzein was used as the internal standard. The method has a lower limit of quantitation of 0.25 mg/L using 200 micro L serum. The intra- and inter-day relative standard deviations calculated from quality control (QC) samples were below 4%. The inter-day relative error was within 1%. Nateglinide serum concentrations in rabbits given nateglinide-hydroxypropyl-beta-cyclodextrin complex were much higher than those given the free drug. Significant difference was observed in main pharmacokinetic parameters of t(max) and C(max) but not AUC(0-t) between the complex and free drug. It was concluded that the absorption rate of nateglinide-HPCD complex was enhanced, compared with that of nateglinide free drug.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2004

Development of a dissolution medium for nimodipine tablets based on bioavailability evaluation.

A marked difference in the dissolution rate between two brands of nimodipine tablets was observed using a newly developed dissolution medium of pH 4.5 acetate buffer containing 0.05% sodium dodecyl sulfate (SDS). However, when pH 4.5 acetate buffer containing 0.3% SDS was used as dissolution medium, which was specified in the edition, the dissolution results of the both brands conformed to the BP requirements and no significant difference in dissolution was observed. The dissolution data obtained for two commercial brands of nimodipine tablets indicate the superiority of the proposed system as a discriminatory dissolution medium for nimodipine tablets. The relative bioavailability of the two brands of nimodipine tablets was determined in healthy adult volunteers after a single dose in a randomized crossover study. Plasma concentrations were determined by a liquid chromatography-tandem mass spectrometry method. Statistical comparison of the AUC(0-T), AUC(0- infinity), C(max), and T(max) indicated a significant difference in the two brands of nimodipine tablets.

Adult↗

PubMed2003

Determination of 3-n-butylphthalide in rabbit plasma by HPLC with fluorescence detection and its application in pharmacokinetic study.

A rapid, sensitive and specific reversed-phase high-performance liquid chromatographic method was developed for the determination of 3-n-butylphthalide, a drug currently being developed for treatment of stroke, in rabbit plasma. Fluorescence detection at an excitation wavelength of 280 nm and an emission wavelength of 304 nm was used for quantification of 3-n-butylphthalide. Ibuprofen was used as internal standard. Plasma samples were extracted with diethyl ether under acidic conditions. After evaporation of the organic phase, the extract was dissolved in mobile phase and injected into the chromatograph with C(18) column and a mobile phase of 0.05 mol/L sodium acetate buffer (pH 4.5)-acetonitrile (400:600). The peak area ratio vs concentration in plasma was linear over the range of 0.0212-4.24 microg/mL (correlation coefficient r = 0.9984) and the limit of quantification was 0.0212 microg/mL. Mean recovery was determined as 101.0% by analysis of plasma standard samples containing 0.0424, 0.424, 2.12 and 4.24 microg/mL of 3-n-butylphthalide. The intra-day relative standard deviations (RSDs) ranged from 3.6 to 8.9% and inter-day RSDs were within 8.0%. Pharmacokinetics of a single intravenous dose of 3-n-butylphthalide to the rabbits was presented to illustrate the applicability of this method. 3-n-Butylphthalide exhibited linear pharmacokinetics after intravenous administration to rabbits over the dose range 1-10 mg/kg.

Aldehydes↗

PubMed2003

Expression and functional involvement of organic anion transporting polypeptide subtype 3 (Slc21a7) in rat choroid plexus.

PURPOSE: It has been shown that transport(s) are involved in the uptake of estradiol 17beta glucuronide (E217betaG) by the choroid plexus (CP). The purpose of this study is to compare the substrate specificity of the transporter in the CP with those of rat organic anion transporting polypeptide 1 (rOatp1) and rOatp3. METHODS: The expression of rOatp1 and rOatp3 in rat CP was confirmed by RT-PCR and Western blot analyses. The substrate specificity of rOatp1 and rOatp3 was compared using cDNA-transfected LLC-PK1 cells. The uptake of E217betaG by rat isolated CP was determined by centrifugal filtration technique. RESULTS: PCR analyses demonstrated that the mRNA expression of rOatp3 was abundant in the CP, whereas that of rOatp1 was low. Immunohistochemical staining revealed that rOatp3 is expressed on the apical membrane of the CP. Kinetic parameters (Km and Ki values) of rOatp3 were similar to those for rOatp1. The results of mutual inhibition study suggest that E217betaG and taurocholate share the same mechanism in the CP. Corticosterone, estrone-3-sulfate and indomethacin are moderate inhibitors, but no effects by digoxin, p-aminohippurate, benzylpenicillin and cimetidine were observed. CONCLUSIONS: rOatp3 is most possible candidate transporter involved in the uptake of organic anions on the brush border membrane of the choroid epithelial cells.

Animals↗