• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.87-90
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• 2012

Cholangiocarcinoma (CCA) is the most common cancer in northeastern Thailand. At present, effective diagnosis of CCA either in humans or animals is not available. Monitoring the development and progression of CCA in animal models is essential for research and development of new promising chemotherapeutics. Ultrasonography has been widely used for screening of bile duct obstruction in CCA patients. In this study, we preliminarily investigated the applicability of ultrasonography to monitor the development and progression of CCA in Syrian golden hamsters (n=8) induced by Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN) administration. Ultrasonography and histopathological examination of hamsters was performed at week 0, 20, 24 and 28 of OV infection or at the start of water/Tween-80 administration to controls. The ultrasonographic images of liver parenchyma and gallbladders of OV/DMN-induced CCA hamsters showed sediments in gallbladder, thickening of gallbladder wall, and hypoechogenicity of liver parenchyma cells. The ultrasonographic images of liver tissues were found to correlate well with histopathological examination. Although ultrasonography does not directly detect the occurrence of CCA, it reflects the thickening of bile ducts and abnormality of liver tissues. It may be applied as a reliable tool for monitoring the development and progression of CCA in animal models in research and development of new promising chemotherapeutics for CCA.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.47-50
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• 1997

Drug development began with the finding of biologically active compounds which are obtained by chemical synthesis or from natural sources. The advent of Combinatorial Chemistry is recognized as a strategy which has a potential to change the methodology of research and development(R&D) of new drugs. Drug development has been carried out with diverse strategies. In the past several decades a variety of new methodology have been introduced in R&D. Random screening of accumulated synthetic samples which had been synthesized for development of other drugs led to the discovery of new drugs. The typical examples are anti-asthma drug trimethoquinol and calcium antagonist diltiazem. (herbesser). In particular the latter drug has been used as a calcium antagonist worldwide, however it was first synthesized to find new tranquilizer and this is the reason why diltiazem has benzodiazepam skeleton. The random screening contributed in the finding of new drugs were carried out with whole animal test and it is a standard methodology in R&D of new drugs. Aspirin is the first synthetic non-steroidal antiinflammatory drug(NSAID) and has been used for more than one hundred years. It is the first example of drug developed from natural product. Salicin is the main constituent of willow bark which had been used in Europe for a long time to treat arthritis and aspirin was developed from salicin. Most of NSAID used clinically were developed from the structure of aspirin, however it took 70 years to clarify why aspirin exhibits its antiinflammatory, analgesic and antipyretic activities. The target of aspirin is cyclooxygenase(COX)which is the first enzyme involved in arachidonate cascade leading to the production of prostaglandins(PG) and thromboxan(TX). Side effect of aspirin causing ulcer in stomach is rather serious problem, since aspirin is so popular drug easily obtained in drug store(OTP). This problem is now going to be solved by a new finding on COX, which have two different types, one is constitutionally expressed COX 1 in almost all organs and the other is inducible COX 2. COX 2 is the responsible enzyme in inflammation etc and now the search of COX 2 specific inhibitors is the target of R&D of next generation NSAID.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.272.1-272.1
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• 2000

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.1-18
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• 2022

Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.411-422
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• 2013

G-protein-coupled receptors (GPCR) are the largest superfamily of receptors responsible for signaling between cells and tissues, and because they play important physiological roles in homeostasis, they are major drug targets. New technologies have been developed for the identification of new ligands, new GPCR functions, and for drug discovery purposes. In particular, intercellular lipid mediators, such as, lysophosphatidic acid and sphingosine 1-phosphate have attracted much attention for drug discovery and this has resulted in the development of fingolimod (FTY-720) and AM095. The discovery of new intercellular lipid mediators and their GPCRs are discussed from the perspective of drug development. Lipid GPCRs for lysophospholipids, including lysophosphatidylserine, lysophosphatidylinositol, lysophosphatidylcholine, free fatty acids, fatty acid derivatives, and other lipid mediators are reviewed.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.297-304
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• 2010

The present work focuses on preparation of olanzapine, orally dispersing tablets by direct compression method. Effect of super disintegrant crospovidone, disintegration time, drug content on in vitro release has been studied. A factorial design was employed in formulating a prompt dispersible tablet. The selected independent variables crospovidone and fmelt showed significant effect on dependent variables i.e. disintegration time and percent drug dissolved. Disintegration time and percent drug dissolved decreased with increase in the level of crospovidone. The similarity factor $f_2$ was found to be 97.48 for the developed formulation indicating the release was similar to that of the marketed formulation. Pharmacokinetics of olanzapine after single-dose oral administration of orally disintegrating tablet in normal volunteers were evaluated and the results showed that PK parameters (Cmax, Tmax, AUC) of the designed ODT matrix were similar to those of commercial product, Zyprexa Zydis$^{(R)}$ as a reference.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.175-175
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• 2001

This experiment tested whether in utero and lactational exposure to 4-nonylphenol (NP) alters mammary gland differentiation in the female offspring rat. Pregnant Sprague Dawley rats were administered NP (l0, 100 mg/kg), atrazine (l00 mg/kg), pesticide demonstrating antiestrogenic activity in mammary gland development, or vehicle (0.5% methyl cellulose) by oral gavage from gestation day 15-19.(omitted)

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.413-418
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• 2004

A bioequivalence of $Melax^{TM}$ capsules (Chong Kun Dang Pharm., Korea) and $Mobic^{TM}$ capsules (Boehringer Ingelheim Korea) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 15 mg dose of meloxicam of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2\;{\times}\;2$ crossover design. Concentrations of meloxicam in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 72 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Melax^{TM}/Mobic^{TM}$ were 0.95 - 1.04 and 0.98 - 1.14, respectively. This study demonstrated a bioequivalence of $Melax^{TM}$ and $Mobic^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.319-325
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• 2004

A bioequivalence of $Etodol^{TM}$ tablets (Yuhan corporation) and $Kuhnillodine^{TM}$ tablets (Kuhnil Pharm. Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 mg dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2{\times}2$ crossover design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Etodol^{TM}/Kuhnillodine^{TM}$ were 1.01-1.10 and 0.87-1.06, respectively. This study demonstrated a bioequivalence of $Etodol^{TM}$ and $Kuhnillodine^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.505-511
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• 2004

A bioequivalence study of $Bestidine^{TM}$ tablets (Choong Wae Pharma. Corp., Korea) to Dong-A $Gaster^{TM}$ (Dong-A Pharmaceutical Co., Ltd., Korea) tablets was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the famotidine dose of 40 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of famotidine were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the Cmax ratio for $Bestidine^{TM}/Gaster^{TM}$ were log 0.90-log 1.06 and log 0.98-log 1.20, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Bestidine^{TM}$ and $Gaster^{TM}$ with respect to the rate and extent of absorption.