| Modelings:
Pharmacokinetic/Pharmacodynamic/Mathematical |
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1) Pharmacokinetic/Pharmacodynamic (PK/PD) modeling |
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a)
Furosemide-induced diuresis and natriuresis in rats and the
effect of plasma albumin |
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b)
Vitellogenin biosynthesis in male trout via estrogen-induced,
receptor-mediated gene induction (biological feedback system) |
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c) Iron metabolism associated with transferrin catabolism
and HFE receptor |
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2)
Biology-based mathematical modeling |
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a)
Periodical expression of reproductive hormones (hormonal feedback) |
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b)
Caspase-dependent signal transduction and apoptosis |
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3)
Pharmacokinetic modeling |
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a)
Albumin and IgG turnover and regulation of albumin and IgG
turnover by FcRn-mediated mechanism in vivo |
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b)
Transferrin turnover and in vivo kinetics and the role of
HFE receptor |
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| Preclinical
pharmacokinetics and pharmacodynamics (PK/PD): Small molecules |
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1)
Pharmacokinetic/Pharmacodynamic analysis |
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a)
PK: compartmental (model-dependent) and non-compartmental
(model-independent) data analysis |
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b)
PD: link (effect compartment) and indirect-response model |
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c)
Physiology-based pharmacokinetics (PBPK) and PBPK/PD link
model |
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2)
In vivo pharmacokinetics and pharmacodynamics |
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a)
PK/PD of loop diuretics after various routes of administration:
intravenous (bolus injection and continuous infusion), intraportal
(bolus injection and continuous infusion), oral, intragastric,
intraduodenal, intrajejunal, and intraileal administration.
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b)
Preclinical
PK (company-joint projects): full ADME or in part |
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i)
Anticancer agent (DA-125): with Dong-A Pharmaceutical Company,
Yongin, South Korea |
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ii) Hepatoprotective
agent (YH439): with Yuhan Research Center of the Yuhan Corporation,
Kunpo, South Korea |
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iii)
Proton pump inhibitor (YJA-20379-8): with Yung Jin Pharmaceutical
Company, Hwasung, South Korea |
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c)
Absorption: bioavailability and intestinal uptake, closed-loop
study, absorption site in GI tract, enterohepatic recycling,
deconvolution model |
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d)
Distribution: tissue distribution and partition coefficients |
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e)
Metabolism: details below |
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f)
Excretion: renal and nonrenal excretion |
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3)
Drug metabolism and disposition |
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a)
In vitro tissue metabolism (liver, kidney, intestine, and
other tissues) |
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b)
Vmax, Km, and CLint of drugs in the microsomal preparation |
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c)
CYP subtype-specific inhibition and induction study in vivo |
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d)
Total CYP activity in the liver and kidney |
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e)
Microsomal fractionation and activity |
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f)
Perfusion of liver and kidney |
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4)
In vitro pharmacokinetics |
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a)
Blood retention or blood storage effect of drugs |
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b)
Partition coefficient between blood and plasma |
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c)
Stability of drug in the biological matrices (plasma, urine,
GI contents) |
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d)
Plasma protein binding: dose-dependency, displacement |
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e)
Development and optimization of HPLC of parent drugs and metabolites |
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f)
Various sample processings for detection: extraction, derivatization,
etc. |
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5)
Nonlinear pharmacokinetics |
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a)
Hepatic and gastrointestinal first-pass effect |
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b)
Lung and heart first-pass effect and drug extraction by organs |
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c)
Dose-dependent pharmacokinetics, reversible metabolism |
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d)
Michaelis-Menten saturable kinetics and combination with a
first-order process |
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e)
Intrinsic organ clearance, organ extraction model |
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6)
PK/PD in pathophysiologic animal models (experimental and
genetic) |
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a)
Diabetes: Alloxan-induced rats, Streptozotocin-induced rats |
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b)
Hypertension: Spontaneous hypertensive rats (SHR), DOCA-induced
rats |
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c)
Liver cirrhosis: Dimethylnitrosamine-induced rats |
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d)
Acute renal failure: Uranyl nitrate-induced rats |
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e)
Hypoalbuminemia: Nagase analbuminemic rats (NAR), FcRn-KO
mice |
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f)
Immunodeficiency: ß2-microglobulin-deficient mice |
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g)
Iron-overload: HFE-deficient mice |
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| Preclinical
pharmacokinetics and pharmacodynamics (PK/PD): Macromolecules |
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1)
In vivo kinetics of protein turnover and production |
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a)
Production and turnover of serum albumin and transferrin in
FcRn-deficient and wild-type mice |
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b)
Turnover of transferrin and IgA in HFE-deficient and wild-type
mice |
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c)
Pharmacokinetics of albumin, transferrin, IgG, and IgA in
?2-microglobulin-deficient and wild-type mice |
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d)
Kinetic decay of biosynthetically-radiolabeled proteins in
FcRn-deficient mice and wild-type mice: serum albumin and
transferrin |
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e)
Kinetic decay of radioiodinated serum proteins in FcRn-deficient
mice and wild-type mice: albumin, transferrin, IgG, and IgA |
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f)
Distribution of radioiodinated albumin, IgA, and IgG in FcRn-deficient
mice and wild-type mice |
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g)
Concentration-dependent catabolism of protein: Receptor-mediated
saturable recycling of protein |
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h)
Controlling plasma IgG level by immunization and vaccination
in the mouse |
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2)
Protein transport |
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a)
Maternofetal transport across placenta (yolk sac) of mouse |
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i) IgG,
albumin, IgA, and transferrin |
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ii) Blood
sampling in both mother and fetus (cardiac puncture) after
C-section |
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b)
Transendothelial flux of proteins by receptor-mediated process,
diffusion, endocytosis, pinocytosis, and bulk-flow |
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| Laboratory
animals and handlings |
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1)
Animal handlings for in vivo pharmacology and pharmacokinetics |
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a)
Animals: mouse, hamster, rat, rabbit, and dog |
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b)
Administration |
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i) Oral:
mouse, rat, rabbit, and dog |
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ii) Intravenous:
bolus injection and infusion; via jugular, femoral, tail,
and cephalic vein |
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iii)
Subcutaneous: injection and infusion by an osmotic pump |
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iv)
Intraperitoneal: injection and infusion by an osmotic pump |
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v) Intraportal:
bolus injection and infusion by a permanent cannulation |
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vi) Intramuscular:
induction of anesthesia or sedation |
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vii)
Intragastric, intraduodenal, intrajejunal, and intraileal
injection |
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c)
Sampling of biological tissues: mouse, rat, rabbit, and dog |
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i) Plasma,
bile acid, urine, feces, gastrointestinal tract, liver, kidney,
spleen, muscle, fat, brain, heart, lung, bone, gallbladder,
skin, etc. |
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d)
Surgery |
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i) Cannulation:
jugular vein (mouse, rat, and rabbit), femoral vein (rat),
portal vein (rat and dog), carotid artery (mouse, rat, and
rabbit), femoral artery (rat), bile duct (rat), marginal ear
vein (rabbit), and cephalic vein (dog) |
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ii) Urinary
catheter: rat, rabbit, and dog |
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e)
Bleeding |
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i) Multiple/continuous
bleeding: carotid artery (mouse, rat, and rabbit), femoral
artery (rat), retroorbital plexus/sinus (mouse and rat), cephalic
vein (dog) |
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ii) Terminal
bleeding: Abdominal aorta (mouse, rat, and rabbit), inferior
vena cava (mouse and rat), and cardiac puncture (mouse and
rat) |
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f)
Fetal surgery |
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i) Fetus
recovery with C-section: at day 19 of pregnant mice |
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ii) Cardiocentesis
from fetus (gestational day 19 and 20) |
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2)
Experience in protocols and maintenance of laboratory animals |
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a)
Animal Use Protocol |
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b)
Mouse husbandry: breeding mouse strains and weaning pups;
tail clip for genotyping; timed-pregnancy; colony maintenance |
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| Preclinical
pharmacology |
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1)
P-glycoprotein (Pgp)-mediated pharmacokinetics and pharmacodynamics |
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a)
Pgp-dependent subcellular distribution of paclitaxel in breast
cancer cells |
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i) Subcellular
fractionation method (nucleus, mitochondria, microsome, and
cytosol) |
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ii) Marker
enzyme/protein assay for the purity of each fraction |
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iii)
Pgp-negative cells and Pgp-overexpressing cells by stable
transfection |
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b)
Pgp-dependent differential apoptosis induced by paclitaxel |
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i) Apoptosis:
caspase-dependent and –independent mechanism |
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ii) Apoptosis
in cell-free system (cell membrane-independent apoptosis) |
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iii)
Nucleus-mediated and Pgp-induced apoptosis |
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c)
Intracellular uptake of anticancer agents |
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i) Pgp
substrates: paclitaxel, vincristine, and vinblastine |
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ii) Pgp
blockers: cyclosporin A, verapamil, and PSC833 (Valspodar) |
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iii)
Cell lines: Caco-2, PC-3, MCF7, BC19, etc |
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2)
Cell biology and cellular pharmacology |
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a)
Mammalian cell culture and maintenance |
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b)
Apoptosis assay: DNA-histone ELISA, DNA fragmentation assay,
caspase-3 assay by colorometry, DNA ladder by DNA gel electrophoresis |
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c)
In vitro cytotoxicity : SRB assay, MTT and XTT assay |
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d)
Light and fluorescence microscopy; Coulter counting |
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e)
H&E staining, DAPI and PI staining |
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| Clinical
pharmacokinetics and pharmacodynamics (PK/PD) |
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1)
Clinical pharmacokinetics: Bioavailability and Bioequivalence |
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2)
Clinical PK/PD analysis: PK/PD modeling of resistance of clinical
diuretics in renal diseases; different routes of administration
(iv bolus and infusion) |
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| Analytical
methods |
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1) Radioisotopes and radiobiology |
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a)
Gamma counting for 125I and 131I |
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b)
Liquid scintillation counting for 3H and 14C |
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c)
Protein labeling: radioiodination (Iodogen method) and reductive
methylation |
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i) Albumin,
transferrin, IgA, and IgG |
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2)
Analytical chemistry of protein and endogenous molecules |
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a)
Analytical and preparative sodium dodecylsulfate-polyacrylamide
gel electrophoresis (SDS-PAGE) |
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b)
Immunology-based approach: ELISA, immunoprecipitation, immunoblot |
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i) ELISA:
mouse albumin, mouse transferrin, mouse IgA, mouse IgG, human
albumin, human IgG, and human ?2-microglobulin, etc. |
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c)
Biochemical chromatography: ion-exchange, affinity chromatography,
etc. |
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d)
Development of ELISA for serum-amyloid protein (SAP) and quantification
of the protein |
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e)
Leucine measurement by HPLC-UV system via derivatization |
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3)
Data analysis and software skills |
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a)
Pharmacokinetic and pharmacodynamic data analysis and modeling/simulation
using WinNonlin®, STELLA® |
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b)
Chromatography Software: Beckman System Gold |
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c)
HPLC system: Waters, Bio-Rad, Beckman |
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d)
Mathematical and statistical computing and analysis: MATLAB,
SPSS, SAS |
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e)
Image analysis: Gel-Doc (Quantity One; Bio-Rad), Phosphorimager |
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f)
Softwares: Microsoft® Excel®, Word®, Power Point®;
SigmaPlot®, Adobe® Photoshop®, EndNote®, Reference
Manager® |
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