In-Hwan Baek

Kyungsung University, Tsau-liang-hai, Busan, South Korea

Are you In-Hwan Baek?

Claim your profile

Publications (29)61.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP) solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS) process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h) and peak plasma concentration (Cmax) increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.
    Molecules 12/2014; 19(12):20325-20339. · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study was undertaken to improve the solubility and dissolution of a poorly water-soluble drug, celecoxib, by surface modification with a hydrophilic polymer and a surfactant by using a spray-drying technique. Based on the preliminary solubility tests, hydroxypropylmethyl cellulose (HPMC) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected as the polymer and the surfactant, respectively. A novel surface-modified celecoxib microparticle was successfully fabricated using a spray-drying process with water, HPMC, and TPGS, and without the use of an organic solvent. The physicochemical properties of the surface-modified celecoxib microparticle were characterized using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), a particle size analyzer, and contact angle determination. The formulation with drug/HPMC/TPGS at the weight ratio of 1:0.5:1.5 was determined to be the most effective composition in the preparation of the surface-modified celecoxib microparticle, based on the results of wettability, solubility, and dissolution studies. We found that the surface modification of microparticles with HPMC and TPGS can be an effective formulation strategy for new dosage forms of poorly water-soluble active pharmaceutical ingredients (APIs) to provide higher solubility and dissolution. Copyright © 2014 Elsevier B.V. All rights reserved.
    International Journal of Biological Macromolecules 10/2014; · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to develop lercanidipine-hydroxypropylmethyl cellulose (HPMC) nanoparticles with high oral bioavailability. The lercanidipine-HPMC nanoparticles with/without surfactants were manufactured using a supercritical antisolvent (SAS) process. Gelucire 44/14, poloxamer 407, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were evaluated as surfactants. Spherical lercanidipine-HPMC nanoparticles with a mean particle size less than 400nm were successfully prepared using a SAS process. The dissolution and oral bioavailability of lercanidipine was significantly increased by addition of surfactants. Especially lercanidipine-HPMC nanoparticles with TPGS showed a 2.47-fold higher oral bioavailability than raw material. Furthermore, the dissolution efficiency was strongly correlated to the in vivo Cmax and AUC0→24h. Therefore, the preparation of HPMC nanoparticles with TPGS using a SAS process is a highly effective formulation strategy for enhanced oral bioavailability of lercanidipine.
    International Journal of Biological Macromolecules 08/2014; · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 1. JHL45, a novel immune modulator against atopic dermatitis (AD), was synthesized from decursin isolated from Angelica gigas. The goal is to evaluate the lead compound using quantitative modeling approaches to novel anti-AD drug development. 2. We tested the anti-inflammatory effect of JHL45 by in vitro screening, characterized its in vitro pharmacokinetic (PK) properties. The dose-dependent efficacy of JHL45 was developed using a pharmacokinetics/pharmacodynamics/disease progression (PK/PD/DIS) model in NC/Nga mice. 3. JHL45 has drug-like properties and pharmacological effects when administered orally to treat atopic dermatitis. The developed PK/PD/DIS model described well the rapid metabolism of JHL45, double-peak phenomenon in the PK of decursinol and inhibition of IgE generation by compounds in NC/Nga mice. Also, a quantitative model was developed and used to elucidate the complex interactions between serum IgE concentration and atopic dermatitis symptoms. 4. Our findings indicate that JHL45 has good physicochemical properties and powerful pharmacological effects when administered orally for treatment of AD in rodents.
    Xenobiotica 05/2014; · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to develop a novel valsartan-loaded spray-dried emulsion based on hydroxypropylmethyl cellulose (HPMC) with enhanced oral absorption. The valsartan-loaded redispersible dry emulsion was prepared by using a high-pressure homogenization and spray-drying process with water, Capryol 90, HPMC, and different surfactants, based on the results of the solubility study. The spray-dried emulsions formed small and homogeneous emulsions with a mean droplet emulsion size ranging from 133.5 to 152.5nm at the dispersion state in water. The valsartan-loaded redispersible dry emulsion with HPMC/poloxamer 407 showed enhanced pH-independent valsartan release, resulting in a dramatically enhanced oral bioavailability of valsartan compared to the raw material and commercial product. Therefore, a formulation strategy using the redispersible dry emulsion with HPMC/poloxamer 407 is very effective for the development of a new dosage form containing valsartan.
    International Journal of Biological Macromolecules 05/2014; · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The objective of the present study was to develop population pharmacokinetic models for olmesartan medoxomil and hydrochlorothiazide and to investigatem the influence of demographic factors on these population pharmacokinetics. Methods: Plasma concentrations of olmesartan medoxomil and hydrochlorothiazide were measured in 41 healthy volunteers enrolled in our bioequivalence study by LC-MS/MS following oral administration of an olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) fixed-dose combination tablet. This data and covariates were subjected to nonlinear mixed-effect modeling analysis using the NONMEM software. Evaluation featured a visual predicted check and bootstrapping. Results: The distributions of olmesartan medoxomil and hydrochlorothiazide were best fitted using a two-compartment model with no lag time and first-order elimination. When analyzing hydrochlorothiazide kinetics, we found that TCHO and CL/F were correlated, while. HB and Ka influenced olmesartan medoxomil modeling. All evaluations indicated that the pharmacokinetic profiles of olmesartan medoxomil and hydrochlorothiazide were adequately described using our PPK model. Conclusions: This study indicates that demographic factors influence the inter-individual variability in the disposition of the combination drug, and it might be more useful to apply it to the PK of olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablets administered to patients with hypertension.
    International journal of clinical pharmacology and therapeutics 05/2014; · 1.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to investigate the effect of particle size on the dissolution and oral absorption of pranlukast microsuspensions and nanosuspensions stabilized by hydroxypropylmethyl cellulose. Four pranlukast suspensions with different mean particle sizes (0.16, 0.89, 3.13, and 18.21μm) were prepared by various top-down processes such as jet milling, high pressure homogenization, and bead milling. The dissolution rate and oral absorption of pranlukast suspensions were significantly affected by the particle size. The in vivo pharmacokinetic parameters of pranlukast suspensions were increased with decreasing mean particle size of suspensions. Especially, the AUC0→24h and Cmax values of pranlukast nanosuspension with a particle size of 0.16μm were approximately 3.5- and 6.3-fold greater, respectively, than that of pranlukast microsuspension with a particle size of 18.21μm. Therefore, the preliminary results from our study suggest that a pranlukast nanosuspension with a mean particle size of about 0.16μm may have significant potential for clinical application.
    International journal of biological macromolecules 03/2014; · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to investigate the effect of Soluplus® on the solubility of atorvastatin calcium and to develop a solid dispersion formulation that can improve the oral bioavailability of atorvastatin calcium. We demonstrated that Soluplus® increases the aqueous solubility of atorvastatin calcium. Several solid dispersion formulations of atorvastatin calcium with Soluplus® were prepared at various drug : carrier ratios by spray drying. Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in each solid dispersion, and the 2 : 8 drug : carrier ratio provided the highest degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in rats revealed that the 2 : 8 dispersion significantly improved the oral bioavailability of atorvastatin. This study demonstrates that spray-dried Soluplus® solid dispersions can be an effective method for achieving higher atorvastatin plasma levels.
    CHEMICAL & PHARMACEUTICAL BULLETIN 01/2014; 62(6):545-51. · 1.38 Impact Factor
  • Source
    Min-Soo Kim, In-Hwan Baek
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan-hydroxypropyl methylcellulose-poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.
    International Journal of Nanomedicine 01/2014; 9:5167-76. · 4.20 Impact Factor
  • Source
    Bulletin- Korean Chemical Society 09/2013; 34(9). · 0.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angelica gigas Nakai and its components are known to have neuroprotective, antiplatelet, and anticancer activities. The present study evaluated the in vitro and in vivo biopharmaceutical characterization of Angelica gigas component substances, including decursin (the main substance), decursinol angelate (decursin isomer), JH714 (ether form of decursin) and epoxide decursin (epoxide form of decursin). Decursin, decursinol angelate and JH714 exhibited acceptable metabolic stability (>50%) in liver microsomes from human and higher bound fraction (>90%) in human plasma operating ultrafiltration. Decursin and decursinol angelate in CYP1A2 and CYP2C19 indicated less than 50% CYP activity, suggesting inhibition of the CYP isoforms using Vivid® CYP screening kit. JH714 only showed an apparent permeability coefficient of 1.5, suggesting good brain/plasma ratio at 0.5, 1, 3, and 5 h. In contrast, Cbrain/Cplasma was 1.5% of the dose remained in GI tract after 8 h, and the excretion rate in urine was
    Drug Development and Industrial Pharmacy 09/2013; 39(10). · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The study of pharmacokinetics of alendronate has been hampered by difficulties in accurately and reproducibly determining their concentrations in serum and urine. Thus, pharmacokinetic characteristics of alendronate have been described in many reports based on urinary excretion data; and plasma pharmacokinetics and the simultaneous pharmacokinetic models of alendronate in plasma and urine are not available. The aims of this study were to measure alendronate concentration in plasma and excretion in urine concurrently and to develop compartmental pharmacokinetic model using urine data. In open-label, single-dose pharmacokinetic study, 10 healthy male volunteers received oral dose of alendronate (70 mg tablet). Blood and urine alendronate concentrations were determined using validated high-performance liquid chromatography method. Non-compartmental analysis was performed using WinNonlin program (Pharsight Inc., Apex, NC). A one-compartment pharmacokinetic model was applied to describe pharmacokinetics of alendronate. A peak plasma alendronate concentration of 33.10 ± 14.32 ng/mL was attained after 1.00 ± 0.16 h. The cumulative amount of alendronate excreted in urine and peak excretion rate were 731.28 ± 654.57 μg and 314.68 ± 395.43 μg/h, respectively. The model, which included first-order absorption rate for oral dosing, showed good fit to alendronate data obtained from plasma and urine. The absorption rate constant was 2.68 ± 0.95 h(-1). The elimination rate constants Kurine and Knon-ur were 0.005 ± 0.004 h(-1) and 0.42 ± 0.08 h(-1), respectively. The pharmacokinetics of alendronate in plasma and urine of healthy men can be predicted using one-compartment model, and thus the behavior of drug in plasma can be estimated from urinary excretion data.
    Drug Development and Industrial Pharmacy 07/2013; · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUR) is a fluoropyrimidine derivative that is activated preferentially in malignant cells by thymidine phosphorylase to form 5-fluorouracil (5-FU). The purpose of this study was to investigate the pharmacokinetic properties of doxifluridine and its two major metabolites, 5-FU, and 5-fluorouridine (5-FUrd), in beagle dogs following a single oral administration of 200 mg doxifluridine capsule (Furtulon(®)). After the administration of 200 mg of Furtulon to 23 beagle dogs, the plasma concentrations of doxifluridine, 5-FU, and 5-FUrd were measured simultaneously, using LC-MS/MS. The parent-metabolite compartment model with first-order absorption and Michaelis-Menten kinetics described the pharmacokinetics of doxifluridine, 5-FU, and 5-FUrd. Michaelis-Menten kinetics sufficiently explained the generation and elimination processes of 5-FU and 5-FUrd. The studies described here are the first to evaluate the relationship between pharmacokinetics of doxifluridine and its metabolites in dogs, and these findings will help in understanding the toxicity mechanism of doxifluridine.
    European Journal of Drug Metabolism and Pharmacokinetics 04/2013; · 1.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract 1. The objectives of this study were to develop a pharmacokinetic model for sarpogrelate and its metabolite M-1 and to identify the effect of food on sarpogrelate and M-1 pharmacokinetics in beagle dogs. 2. A single 100 mg oral dose of sarpogrelate was administered to fasted and fed beagle dogs and the plasma concentrations of sarpogrelate and M-1 were measured simultaneously by liquid chromatography tandem mass spectrometry. The resultant data were analyzed by modeling approaches using ADAPT5. 3. The plasma concentration time course of sarpogrelate and M-1 were described using a parent-metabolite compartment model with first-order absorption and elimination. The systemic exposure of sarpogrelate and its metabolite after the administration of a single 100 mg oral dose was significantly decreased under the fed condition compared to that under the fasting condition. Modeling approaches have sufficiently explained the food effect of sarpogrelate, i.e. an increased Vc and decreased Ka, in fed dogs. The food effect of sarpogrelate was due to its pH-dependent dissolution. 4. These findings suggest that food intake affects both the rate and extent of absorption of sarpogrelate, and that the pharmacological effect of sarpogrelate can differ significantly according to food intake.
    Xenobiotica 03/2013; · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to determine population-based pharmacokinetics parameters for ethanol following multiple intake and to identify the factors influencing the pharmacokinetics. Three different solutions of alcoholic liquor (ethanol 55.39 ± 0.45 g) with different dissolved oxygen concentrations were administered, and blood alcohol concentration was determined in 59 healthy subjects using a breath analyzer. Samples (n = 2955) were collected at various time points. Population pharmacokinetic modeling was performed to describe the pharmacokinetics of ethanol. The influence of individuals' demography and dissolved oxygen concentration was investigated, and Visual Predictive Check and bootstrapping were conducted for internal evaluation. The developed model was used to perform simulations to visualize the effects of covariates on individuals. A one-compartment model with Michaelis-Menten elimination kinetics described the multiple ethanol intake data. Population pharmacokinetic estimates of V(max) and K(m) were 3.256 mmol min(-1) and 0.8183 mmol L(-1), respectively. V(d)/F was estimated to be 77.0 L, and K(a) was 0.0767 min(-1). Body weight, age, and the dissolved oxygen concentration were confirmed to be significant covariates. The mean estimates from the developed population pharmacokinetic model were very similar to those from 500 bootstrap samples, and Visual Predictive Check showed that approximately 94% of the observed data fit well within the 5th-95th percentile. A one-compartment model with nonlinear elimination kinetics for multiple ethanol intake was developed and the significant covariates were determined. The robustness of the developed model was evaluated by bootstrap and Visual Predictive Check. The final model and implanted covariates explained well the variability and underlying mechanism of ethanol PK.
    Alcohol (Fayetteville, N.Y.) 01/2013; · 2.41 Impact Factor
  • Jung-Woo Chae, In-Hwan Baek, Kwang-Il Kwon
    [Show abstract] [Hide abstract]
    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Decursin is used as a traditional Asian medicine to treat various women's diseases. AIM OF THE STUDY: Herb-drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of decursin, on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. MATERIALS AND METHODS: After decursin pretreatment for 3 days, on the fourth day rats were administered decursin and theophylline concomitantly. The blood theophylline and its major metabolites (1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (1,3-DMU)) levels were monitored with LC-MS/MS. RESULTS: The results indicated that the clearance, elimination rate constant (K(el)) of theophylline was significantly decreased and area under concentration-time curve (AUC), C(max), half-life was increased in decursin (25mg/kg) pretreatment when theophylline (10mg/kg) was given. In the presence of decursin, the pharmacokinetic parameters of three metabolites (1-MX, 1,3-DMU, and 1-MU) were affected and the differences were statistically significant about AUC(24)(h) parameter. CONCLUSION: Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb-drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy.
    Journal of ethnopharmacology 09/2012; · 2.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Metformin, a biguanide glucose lowering agent, is commonly used to manage type 2 diabetes. • The molecular mechanisms of metformin have not been fully identified, but turnover of biomarkers such as glucose and signalling pathways or translocation of glucose transporters are closely related to the glucose-lowering effects of metformin. • The PK/PD of metformin have been investigated in healthy humans and patients with type 2 diabetes mellitus and modelling has been performed using an indirect response model. WHAT THIS STUDY ADDS • The purpose of this investigation was to develop a population PK/PD model for metformin using a signal transduction model in healthy humans and predict the PK/PD profile in patients with type 2 diabetes. • The aim was to compare a previous model (a biophase model) with the signal transduction model, and use a more appropriate model to follow the actions of metformin. • Additionally, our developed model was appropriate to predict the time course of plasma metformin and fasting plasma glucose (FPG) concentrations in patients with type 2 diabetes. • To our knowledge, this is the first published population PK/PD analysis using the signal transduction model for metformin. AIMS To develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for metformin (500 mg) using the signal transduction model in healthy humans and to predict the PK/PD profile in patients with type 2 diabetes. METHODS Following the oral administration of 500 mg metformin to healthy humans, plasma concentrations of metformin were measured using LC-MS/MS. A sequential modelling approach using NONMEM VI was used to facilitate data analysis. Monte Carlo simulation was performed to predict the antihyperglycaemic effect in patients with type 2 diabetes. RESULTS Forty-two healthy humans were included in the study. Population mean estimates (relative standard error, RSE) of apparent clearance, apparent volume of distribution and the absorption rate constant were 52.6 l h(-1) (4.18%), 113 l (56.6%) and 0.41 h(-1) , respectively. Covariate analyses revealed that creatinine clearance (CL(CR) ) significantly influenced metformin: CL/F= 52.6 × (CL(cr) /106.5)(0.782) . The signal transduction model was applied to describe the antihyperglycaemic effect of metformin. The population means for efficacy, potency, transit time and the Hill coefficient were estimated to be 19.8 (3.17%), 3.68 µg ml(-1) (3.89%), 0.5 h (2.89%) and 0.547 (9.05%), respectively. The developed model was used to predict the antihyperglycaemic effect in patients with type 2 diabetes. The predicted plasma glucose concentration value was similar to previous values. CONCLUSIONS The population signal transduction model was developed and evaluated for metformin use in healthy volunteers. Model evaluation by non-parametric bootstrap analysis suggested that the proposed model was robust and parameter values were estimated with good precision.
    British Journal of Clinical Pharmacology 03/2012; 74(5):815-23. · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angelica gigas NAKAI is used to treat dysmenorrhea, amenorrhea, menopause, abdominal pain, injuries, migraine, and arthritis. The present study provided a physicochemical and toxicological characterization of compounds in A. gigas NAKAI (decursin, decursinol angelate, diketone decursin, ether decursin, epoxide decursin and oxim decursin). Diketone decursin (173.16 μg/mL) and epoxide decursin (122.12 μg/mL) exhibited >100 μg/mL kinetic solubility after applying nephelometry, suggesting a highly soluble compound. The Student’s t-test revealed significant differences in the pKa ranges of the compounds by automatic titration from capillary electrophoresis (p<0.05). Diketone decursin, epoxide decursin and oxim decursin might be formulated into an oral dosage form (log P: 0-3) by an automatic titration analysis. A parallel artificial membrane permeability assay demonstrated permeability coefficients of <10 x 10⁻⁶ cm/s for all of the compounds, suggesting poor permeability. Ether decursin exhibited a toxic effect after being applied to mouse (NIH 3T3, EC₅₀: 57.9 μM) and human (HT-29, EC₅₀: 36.1 μM; Hep-G2, EC₅₀: 4.92 μM) cells. Additionally, epoxide and oxim decursin were toxic through acute oral toxicity (four and three deaths of Institute of Cancer Research (ICR) mice) and mutation toxicity testing by applying Salmonella typhimurium cells with and without S9. Although diketone decursin exhibited less permeability, it is potentially valuable pharmacological compound that should be investigated.
    Biological & Pharmaceutical Bulletin 01/2012; 35(7):1084-90. · 1.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An enteric-coated formulation of triflusal (triflusal EC), an antiplatelet agent, was developed to reduce the high incidence of gastrointestinal adverse events (AEs). The aim of this study is to compare the pharmacokinetics, pharmacodynamics and safety of triflusal EC with triflusal in healthy Korean male subjects to determine bioequivalence and non-inferiority for the purposes of marketing approval. A randomized, open-label, two-period, crossover study was conducted in 38 subjects. Either triflusal EC or triflusal was administered orally as a single 900 mg loading dose (day 1) followed by eight 600 mg/day maintenance doses on days 2 - 9, with a 13-day washout period. The plasma concentrations of 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), the predominant active metabolite of triflusal, were assessed after administration of the loading dose, using HPLC/MS/MS. The platelet aggregation response to arachidonic acid was determined using turbidimetric aggregometry. The 90% CIs, for the geometric mean ratios of the log-transformed AUC(τ) and C(max) of HTB were seen to be within the predetermined range of 0.8 - 1.25. Triflusal EC was also shown to be non-inferior in its anti-aggregatory effect. No serious AEs were reported during this study. The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated.
    Expert Opinion on Drug Metabolism &amp Toxicology 12/2011; 7(12):1471-9. · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nitric oxide (NO) is synthesized from L-arginine (Arg) by NO synthase (NOS), and asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO formation. Normal distribution values of Arg, ADMA, and SDMA are required to evaluate the effects of cardiovascular drugs on blood vessels, but insufficient normal reference values from rat and mouse plasma exist for new drug development and screening. To determine the means and variations in the basal endogenous materials concentration, Arg, ADMA, and SDMA in blank rat (n = 24) and mouse (n = 37) plasma samples were quantified using LC-MS/MS equipped with an electrospray ionization interface to generate positive mode ions. Accuracy and precision were within 90.42-110.91%, and 0.88-13.84%, respectively, for analyses of Arg, ADMA, and SDMA. The average plasma concentrations of Arg, ADMA, and SDMA were 175.38 +/- 13.87 microM, 0.79 +/- 0.20 microM, and 0.84 +/- 0.20 microM, respectively, in rats and 70.81 +/- 19.38 microM, 0.66 +/- 0.21 microM, and 0.42 +/- 0.10 microM, respectively, in mice. These results will provide a basis on which to evaluate cardiovascular drug effects on ARG, ADMA, and SDMA levels in new drug development.
    Arzneimittel-Forschung 06/2011; 61(6):340-6. · 0.51 Impact Factor

Publication Stats

36 Citations
61.93 Total Impact Points


  • 2014
    • Kyungsung University
      • College of Pharmacy
      Tsau-liang-hai, Busan, South Korea
  • 2007–2013
    • Chungnam National University
      • College of Pharmacy
      Seongnam, Gyeonggi, South Korea
  • 2010
    • Chonbuk National University
      Tsiuentcheou, North Jeolla, South Korea