Myoung-Gyu Lee

Comparative bioavailability of silibinin in healthy male volunteers.

AIM To study a comparative bioavailability of Liverman capsule to Legaion capsule and Silymarin tablet (which contain silibinin) in 24 healthy volunteers. VOLUNTEERS AND METHODS Twenty-four healthy male Korean volunteers received each medicine at the silibinin dose of 120 mg in a 3 x 3 crossover study. There was a 1-week washout period among the doses. Plasma concentrations of silibinin were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated by the trapezoidal rule extrapolation method. Cmax (maximum plasma drug concentration) and tmax (time to reach a Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf, AUC(0-12h), and Cmax and untransformed tmax. RESULTS After an oral administration of Liverman capsule, the pharmacokinetic parameters of silibinin, such as AUC(0-12h) (5.59, 4.24 and 13.9 microg/ml x h for Legalon capsule, Silymarin tablet and Liverman capsule, respectively) and AUCinf (6.00, 4.63 and 15.1 microg/ml x h) were significantly greater, Cmax (1.33, 1.13 and 6.04 microg/ml) was significantly higher and tmax (1.83, 2.10 and 0.875 h) was significantly faster than those after Legalon capsule and Silymarin tablet. CONCLUSION These results indicate that the absorption and the extent of relative oral bioavailability of silibinin after Liverman capsule were significantly faster and greater, respectively, than those after Legalon capsule and Silymarin tablet.

Mechanical Behavior of AZ31B Mg Alloy Sheets under Monotonic and Cyclic Loadings at Room and Moderately Elevated Temperatures

Large-strain monotonic and cyclic loading tests of AZ31B magnesium alloy sheets were performed with a newly developed testing system, at different temperatures, ranging from room temperature to 250 °C. Behaviors showing significant twinning during initial in-plane compression and untwinning in subsequent tension at and slightly above room temperature were recorded. Strong yielding asymmetry and nonlinear hardening behavior were also revealed. Considerable Bauschinger effects, transient behavior, and variable permanent softening responses were observed near room temperature, but these were reduced and almost disappeared as the temperature increased. Different stress–strain responses were inherent to the activation of twinning at lower temperatures and non-basal slip systems at elevated temperatures. A critical temperature was identified to account for the transition between the twinning-dominant and slip-dominant deformation mechanisms. Accordingly, below the transition point, stress–strain curves of cyclic loading tests exhibited concave-up shapes for compression or compression following tension, and an unusual S-shape for tension following compression. This unusual shape disappeared when the temperature was above the transition point. Shrinkage of the elastic range and variation in Young’s modulus due to plastic strain deformation during stress reversals were also observed. The texture-induced anisotropy of both the elastic and plastic behaviors was characterized experimentally.

Measurements of anisotropic yielding, bauschinger and transient behavior of automotive dual-phase steel sheets

In order to present better prediction capability in computational analysis, mechanical properties of the dualphase high strength steel have been characterized especially for anisotropy as well as the Bauschinger and transient behavior. As for the anisotropy, the non-quadratic anisotropic yield function Yld2000-2d has been utilized and its material parameters have been obtained using the uni-axial tension tests as well as the hydraulic bulge test. To measure the hardening behavior including the Bauschinger and transient behavior, a newly developed test method has been applied for the uni-axial tension/compression and compression/tension tests, in which solid blocks along the both sides of the sheet specimen prevent buckling. From the tension/compression curves, the equations to describe isotropic and kinematic hardening behavior have been obtained. The modified Chaboche model has been confirmed to well represent the hardening behavior including the Bauschinger and transient behavior.

Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Korean subjects.

OBJECTIVE This study aimed to evaluate the effect of genetic polymorphisms of SLCO1B1 and ABCB1 on the pharmacokinetics of atorvastatin and its metabolites. METHODS 290 Koreans were genotyped for SLCO1B1, ABCB1 and CYP3A5, and 28 subjects were selected for the pharmacokinetic study. Each subject received a single oral dose of 20 mg atorvastatin and blood samples were collected up to 48 hr after dosing. The relationship between the genotypes and atorvastatin pharmacokinetics was examined. RESULTS For SLCO1B1 genotypes, the mean area under the concentration-time curve from time 0 to infinity (AUC0-infinity) of atorvastatin was 148.2 ng x hr/ml for *15/*15 subjects (n = 3), which was significantly larger than for 1a/*15 and *1b/*15 (n = 8) (80.7 ng x hr/ml, p = 0.0121) and also larger than for *1a/*1a, *1a/*1b and *1b/*1b (n = 17) (66.3 ng x hr/ml, p = 0.0018). The mean AUC0-infinity of 2-hydroxyatorvastatin for *15/*15 was also larger than in *1a/*1a, *1a/*1b and *1b/*1b (p = 0.012). In lactone forms, no significant pharmacokinetic difference was found among the genotypes. For ABCB1 genotypes, the half-lives of atorvastatin, atorvastatin lactone, 2-hydroxyatorvastatin and 2-hydroxyatorvastatin lactone were significantly longer in c.2677TT-c.3435TT (n = 3) vs. c.2677GG-c.3435CC and c.2677GT-c.3435CT (n = 10), yielding p = 0.049, 0.007, 0.007 and 0.007, respectively. CONCLUSION This study shows that the SLCO1B1*15 allele may be associated with the individual difference in the AUC0-infinity of atorvastatin whereas the ABCB1 TT-TT diplotype may affect the elimination half-life of the drug in the Korean population.

Combined isotropic-kinematic hardening laws with anisotropic back-stress evolution for orthotropic fiber-reinforced composites

In order to describe the Bauschinger and transient behavior of orthotropic fiber-reinforced composite solids, a combined isotropic-kinematic hardening law based on the non-linear kinematic hardening rule was considered here, in particular, based on the Chaboche type law. In this modified constitutive law, the anisotropic evolution of the back-stress was properly accounted for. Also, to represent the orthotropy of composite materials, Hills 1948 quadratic yield function and the orthotropic elasticity constitutive equations were utilized. Furthermore, the numerical formulation to update the stresses was also developed based on the incremental deformation theory for the boundary value problems. Numerical examples confirmed that the new law based on the anisotropic evolution of the back-stress complies well with the constitutive behavior of highly anisotropic materials such as fiber-reinforced composites.

Twinning-Slip Transitions in Mg AZ31B

Many metals, particularly ones with hexagonal close-packed (HCP) crystal structures, undergo deformation by combinations of twinning and slip, the proportion of which depends on variables such as the temperature and strain rate. The typical techniques to reveal such mechanisms rely on metallography, X-ray diffraction, or electron optics. Simpler, faster, less expensive mechanical tests were developed in the current work and applied to Mg AZ31B. The curvature of compressive stress–strain plots over a fixed strain range was found to be a consistent indicator of twinning magnitude, independent of the temperature and strain rate. The relationship between the curvature and areal fraction of twins was determined. The transition temperatures determined based on stress–strain curvature were consistent with the ones determined by metallographic analysis and flow stresses, and the results depended on the strain rate according to the Zener-Hollomon parameter, a critical value for which was measured. The transition temperature was found to depend significantly on the grain size, a relationship for which was established. Finally, it was shown that the transition temperature can be determined consistently, and much faster, using a single, novel “step-temperature” test.

Semi-Analytic Hybrid Method to Predict Springback in the 2D Draw Bend Test

A simplified numerical procedure to predict springback in a 2D draw bend test was developed based on the hybrid method which superposes bending effects onto membrane solutions. In particular, the procedure was applied for springback analysis of a specially designed draw bend test with directly controllable restraining forces. As a semi-analytical method, the new approach was especially useful to analyze the effects of various process and material parameters on springback. The model can accommodate general anisotropic yield functions along with nonlinear isotropic-kinematic hardening under the plane strain condition. For sensitivity analysis, process effects such as the amount of bending curvature, normalized back force and friction, as well as material property effects such as hardening behavior including the Bauschinger effect and yield surface shapes were studied. Also, for validation purposes, the new procedure was applied for the springback analysis of the dual-phase high strength steel and results were compared with experiments.

Decoupling Thermal and Electrical Effect in an Electrically Assisted Uniaxial Tensile Test Using Finite Element Analysis

Application of intermittent electric pulses during uniaxial tensile test changes the mechanical behavior owing to electroplastic effect. The electric current increases the temperature of the specimen due to Joule heating. It is, therefore, necessary to decouple the thermal effect from the overall behavior to understand the contribution of electric current in the mechanical behavior. In the present work, an electro-thermo-mechanical finite element study of an electrically assisted uniaxial tensile test of Al5052 alloy is performed to isolate the thermal effect. The simulated results yielded the thermal effect due to the electric current. By comparing the experimental and simulated results, the contribution of electric current is decoupled from that of thermal effect. It is found that the thermal component contributes significantly to the instantaneous stress drop and long-range permanent softening observed in experiment. The electric current, in addition to the instantaneous stress drop and permanent softening, affects the reloading behavior. The present work can be utilized to develop simpler constitutive models for the mechanical behavior of metals subjected to pulsed electric current.

A Novel Multi-objective Genetic Algorithms-Based Calculation of Hill’s Coefficients

The anisotropic coefficients of Hill’s yield criterion are determined through a novel genetic algorithms-based multi-objective optimization approach. The classical method of determining anisotropic coefficients is sensitive to the effective plastic strain. In the present procedure, that limitation is overcome using a genetically evolved meta-model of the entire stress strain curve, obtained from uniaxial tension tests conducted in the rolling direction and transverse directions, and biaxial tension. Then, an effective strain that causes the least error in terms of two theoretically derived objective functions is chosen. The anisotropic constants evolved through genetic algorithms correlate very well with the classical results. This approach is expected to be successful for more complex constitutive equations as well.

Bioequivalence of clarithromycin tablet formulations assessed in Korean males

AIM Determination of the bioequivalence of 2 clarithromycin tablet formulations manufactured in Korea. PATIENTS AND METHODS Twenty-four healthy male Korean volunteers received each of the 2 clarithromycin formulations at a dose of 250 mg in a 2 x 2 crossover study. There was a one-week washout period between doses. Plasma concentrations of clarithromycin were monitored by high-performance liquid chromatography over a period of 12 hours after administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated using the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf and Cmax and untransformed Tmax. RESULTS The point estimates and 90% confidence intervals for AUCinf (parametric) and Cmax (parametric) were 0.971 (0.886 approximately 1.063) and 0.982 (0.868 approximately 1.107), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. The corresponding value of Tmax was 0.000 (-0.250 approximately 0.250). CONCLUSION These results indicate that the 2 medications of clarithromycin are bioequivalent and, thus, may be prescribed interchangeably.