• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.215-221
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• 2003

A bioequivalence study of $Ambrect^{TM}$ tablets (Dong Wha Pharm. Ind. Co., Ltd.) to $Mucopect^{TM}$ tablets (Boehringer Ingelheim Korea, Ltd.) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korea volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography for over a period of 24 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calulated 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 $C_{max}$ ratio for $Ambrect^{TM}/Mucopect^{TM}$ were 0.89-1.01 and 0.89-1.02, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Ambrect^{TM}\;and\;Mucopect^{TM}$ with respect to the rate and extent of absorption.

• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.344-350
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• 1996

Purpose : Noninvasive imaging of tumor cell proliferation could be helpful in the evaluation of tumor growth potential and could provide an early assessment of treatment response. Radiolabeled thymidine, uridine and adenosine have been used to evaluate tumor cell proliferation. These nucleoside analogs are incorporated into DNA during proliferation. Iodine-131-Iodomethyluridine, an analog of Iodine-131-Iododeoxyuridine, is also involved in DNA/RNA synthesis. The purpose of this study was to develop Iodine-131-Iodomethylurdine and image tumor proliferation using Iodine-131-Iodomethyluridine. Materials and Methods : Radiosynthesis of Iodine-131-5-Iodo-2'-O-methyluridine (Iodine-131-Iodomethyluridine) was prepared from 10 mg of 2'-O-methyluridine(Sigma chemical Co., St. Louis, Missouri) and 2.1 mCi(SP. 10Ci/mg) of Iodine-131-labeled sodium iodide in $100{\mu}l$ of water using iodogen reaction. Female Fischer 344 rats were inoculated in the thigh area with breast tumor cells(13765 NF, $10^5$ cells/rat S.C.). After 14 days, the Iodine-131-Iodomethyluridine $10{\mu}Ci$ was injected to three groups of rats(3/group). The percent of injected dose per gram of tissue weight was determined at 0.5-hours, 2-hours, 4-hours, and 24-hours respectively. Tumor bearing rats after receiving Iodine-131-Iodomethyluridine($50{\mu}Ci$ IV) were euthanized at 2 hours after injection. Autoradiography was done using freeze-dried $50{\mu}m$ coronal section. After injection of Iodine-131- Iodomethyluridine ($10{\mu}Ci$/rat, IV) in three breast tumor-bearing rats, planar scintigraphy was taken at 45 minutes, 90 minutes and 24 hours. Results : Iodine-131-Iodomethyluridine was conveniently synthesized using iodogen reaction. The biodistribution showed fast blood clearance and the tumor-to-tissue uptake ratios showed that optimal imaging time was at 2 hours postinjection. Autoradiogram and planar scintigram indicated that tumor could be well visualized. Conclusion : The findings suggest that Iodine-131-Iodomethyluridine, a new radio-iodinated nucleoside, has potential use for evaluation of active regions of tumor growth.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.246-246
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• 1996

The glucuronide conjugates of morphine have been claimed to exert significant neuropharmacological effects. Morphine-6-glucuronide (M6G) may be a potent opioid agonist in vivo, and morphine-3-glucuronide (M3G) may act as a weak opioid antagonist. The present study addressed the permeability of the blood-brain barrier (BBB) for these metabolites compared to morphine. Tracers were prepared by enzymatic glucuronidation of U-methyl-$^3$H]-morphine. Brain uptake in rats was measured by the internal carotid artery perfusion technique and after i.v. bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52${\pm}$0.61 ${\mu}$L min$\^$-1/ g$\^$-1/ Uptake seems to be mediated by passive diffusion and was not saturable by 100 ${\mu}$M morphine in the perfusate. The BBB permeability of [$^3$H]-M3G and [$^3$H]-M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [$^3$H]-M3G and [$^3$H]-M6G 60 min after i.v. bolus injection reached 0.0060${\pm}$0.0003 and 0.0030${\pm}$0.0005% injected dose per g, respectively. From these brain concentrations and from the corresponding plasma concentration - time curves, BBB PS values of 0.14${\pm}$ 0.02 ${\mu}$L min$\^$-1/g$\^$-1/ and 0.11 ${\pm}$ 0.01 ${\mu}$L min$\^$-1/g$\^$-1/, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of MSG explains, why it is approximate]y equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.

• Parasites, Hosts and Diseases
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• v.23 no.1
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• pp.33-40
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• 1985

Two cases of human Erhinostoma hortense infection and their probable infection source were identified by prasiqantel (Distocide) treatment of the patients and by examining two kinds of fresh water fish which were eaten raw by them. The result of the research can be summarized as follows: 1. The patients, each aged 31 and 30, were residing in the same house in Wonju City, Kangwon Province. The first case was hospitalized due to epidemic hemorrhagic fever (E.H. fever) and the second case was healthy but had slight degree of abdominal pain and diarrhea from time to time. In the stool examination, eggs of 5. hortense ($114.3{\times}71.0{\mu\textrm{m}}$) average from the first case and $119.1{\times}68.3{\mu\textrm{m}}$ average from the second) were found. By administering single dose of praziquantel (10~15mg/kg) and purgation with magnesium salt to them. sin adults of 5. hortense were collected from the diarrheal stools of the second case. 2. By examining 8:k Moroco oxycephalus and 20 Carassius carassius which were captured at the place where the two patients had captured and eaten the fresh water fish, the metacercariae of Echinostoma sp. were found from 3 (3.5%) M. oxycephalus. 3. After the experimental infection of 3 isolated metacercariae to one albino rat three adults of 5. hortense were recovered. By the present study, the two patients revealing the echinostomatid eggs in their stools were proven to be infected with 5. hortense and to be the second and third human cases of this luke infection in Korea. Mcroco oxycephalus harboured the metacercariae of E. hortense and appeared to be a new second intermediate host.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.503-512
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• 2001

Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

• Korean Journal of Soil Science and Fertilizer
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• v.2 no.1
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• pp.69-73
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• 1969

In order to improve nearly unarable soils, poor in humus and poorly drained coarse textured, derived from fluvio marine deposit; a factorial experiment have been conducted to find out the influence of compost, increased potassium application and split application of potassium on the yield and germination of soybean variety Haman. The result obtained arid discussed may be summarized as follows. (1) The soybean yield increase was significant by the application of compost, increased amount of potassium and split application of potassium. (2) The application of compost significantly increased the numbers of germination. (3) The increased amount of potash and split application of potash fertilizer showed an apparent effect on the increase of germination and grain numbers per plant. (4) There was a positive relation between the number of grains per plant and the number of pods per plant, however, the increased numbers of pods per plant has not a direct effect for the increase of soybean yield per unit area. (5) Above results suggests that the improvement of nearly unarable Woolsuk Island soils derived from fluvio marine coarse material may be possible by the application of compost, increased amount and split application of potash fertilizer.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.37 no.4
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• pp.383-396
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• 1992

In order to find out the reasons for the excessive accumulation of certain fertilizer elements in arable land in Korea, which may be a detrimental factor for her sustainable agriculture in the future, total requirement of fertilizers were estimated from the huge number of soil test data obtained throughout the country using the fertilizer requirement models based on the soil analysis data and the concepts of multi nutrient factor balance or starter fertiliazer. The total fertilizer requirements estimated based on the present soil fertility status were much less than those estimated from the suspected cropping area of various crops cultivated depending on the conventional fertilizer recommendation for each crops or the actual amount of fertilizer elements consumed through National Agricultural Cooporative Federation(NACF). The excessive accumulation of certain fertilizer elements in arable land in Korea must be due to excessively high dose of chemical fertilizers as well as those farm wastes such as animal wasts produced unexpectedly in large amounts or crop residues. And it is suggested that the improved fertilizer recommendation must be developed in consideration both with the soil fertility status and the amounts of nutrient removal by each crop, and that the high analyzed complex fertilizers commonly used by farmers must ugently be developed in a form containing low P and K with Mg and slow release type N for the better balanced management practices of soil fertility by farmers arid for their practices of sustainable agriculture.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.197-203
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• 2007

A bioequivalence study of $Dilast^{TM}$ Capsule (Chong Kun Dang Pharma. Co., Ltd.) to $Ketas^{(R)}$ Capsule (Han Dok Pharma. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty eight healthy male Korean volunteers received each medicine at the ibudilast dose of 20 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of ibudilast were monitored by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 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 $C_{max}$ ratio for $Dilast^{TM}$ $Capsule/Ketas^{(R)}$ Capsule were $log0.93{\sim}log1.06$ and $log0.93{\sim}log1.11$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Dilast^{TM}$ Capsule and $Ketas^{(R)}$ Capsule with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.65-71
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• 2009

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.73-78
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• 2009

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.