• 한국임상약학회지
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• 제7권1호
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• pp.17-21
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• 1997

Cefaclor is a second generation cephalosporin antibiotic that shows a potent antibacterial activity against both Gram-positive and Gram-negative bacteria, when it is orally administered. Due to its patent expiration, a number of generic drugs have been marketed, but not yet elucidated to ensure therapeutic equivalence. In this study, cefaclor capsules manufactured by Chong Kun Dang were bioequivallently assessed by comparing with $Ceclor^{TM}$ introduced originally by Daewoong Lilly. A total of 16 healthy male volunteers were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of cefaclor in plasma were measured upto 6 hours following a single oral administration of two capsules (500 mg of cefaclor) by high-performance liquid chromatography with UV detection. Although the plasma concentration at 6 hours was not detected, the computed half-life of cefaclor was approximately 0.5 hours. The area under the concentration-vs-time curve from 0 to 4 hours $(AUC_{0-4h})$ was calculated by the trapezoidal summation method. The differences in mean values of $AUC_{0-4h}$, peak plasma concentration $(C_{max})$, and time to peak concentration $(T_{max})$ between the two products were $4.63\%,\;1.84\%,\;and\3.28\%$, respectively. The least significant differences at $\alpha4= 0.05 for $AUC_{0-4h},\;C_{max},\;and\;T_{max}\;were\;6,53\%,\;4.05\%,\;and\;6.47\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

• 한국임상약학회지
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• 제13권2호
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• pp.55-58
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• 2003

Astromicin is an aminoglycoside antiviotic that is structually different from conventional aminoglycosides. Astromicin has been shown to be active against aerobic Gram-negative bacilli. The pharmacokinetics of astromicin were determined in 12 healthy volunteers ($65.5\pm5.23\;kg$ of body weight) following a 30-min continuous intravenous infusion at a dose of 200 mg. The plasma and urine samples were collected up to 24 h and drug concentrations were measured by a bioassay using Bacillus subtilis. Pharmacokinetic parameters were calculated by fitting individual concentration-time curve to a one-exponential decay model. The plasma levels were $16.9\pm1.68\;and\;1.05\pm0.346\l{\mu}g/ml$ at 0 h and 8 h after the infusion, respectively. The elimination half-life of astromicin was $1.86\pm0.360\;h$ The volume of distribution was $0.182\pm0.0164\;L/kg$, and the total body clearance was $5.25\pm1.74\;L/h$. These pharmacokinetic parameters were similar to these of gentamicin, tobramycin, and amikacin. Therefore, it is recommended that therapeutic drug monitoring of astromicin could be conducted in a similar fashion as the other aminoglycosides.

• BMB Reports
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• 제33권2호
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• pp.184-187
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• 2000

Prostaglandin $E_2$ ($PGE_2$) plays an important role in the regulation of various gastric functions, and the growth-inhibitory activities on tumor cells are studied in vitro and in vivo. Although the mechanisms have attracted many researchers in the past decade, the molecular mechanisms of cell cycle arrest, or induction of apoptosis by $PGE_2$, is unclear. We investigated the effects of $PGE_2$ on the growth of the human gastric carcinoma cell line SNU1 and genes that are regulated by $PGE_2$ and isolated them using differential display RT-PCR (DD RT-PCR). FACS analysis suggested that SNU1 cells were arrested at the G1 phase by $PGE_2$ treatment. This growth inhibitory effect was in a time- and dose-dependent manner. Treatment of SNU1 cells with $10\;{\mu}g/ml$ $PGE_2$, followed by DD RT-PCR analysis, revealed differently expressed bands patterns from the control. Among the differently expressed clones, we found an unidentified cDNA clone (HGP-27) overexpressed in $PGE_2$-treated cells. The full-length cDNA of HGP-27 was isolated using RACE, which consisted of a 30-nt 5'-noncoding region, a 891-nt ORF encoding the 296 amino acid protein, and a 738-nt 3'-noncoding region including a poly(a) signal. This gene was localized on the short arm of chromosome number 11. Using the Motif Finder program, a myb-DNA binding repeat signature was detected on the ORF region. The COOH-terminal half was shown to have similarity with the $NH_3$-terminal domain of thioredoxin (Trx). This relation between HGP-27 and Trx implied a potential role for HGP-27 in modulating the DNA binding function of a transcription factor, myb.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.51-53
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• 2003

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets

• The Korean Journal of Pain
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• 제18권2호
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• pp.218-221
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• 2005

This report describes a case of dizziness in a patient with trigeminal neuralgia that was caused by a vestibular schwannoma. A 60-year-old man with a history of pain on his left cheek, chin, molar and tongue for 5 months was diagnosed as suffering with trigeminal neuralgia of the left mandibular nerve, and this was caused by a left vestibular schwannoma. The diagnosis of the tumor was confirmed with magnetic resonance imaging (MRI), and so gamma knife surgery was performed 1 month later. At that time, the patient had been referred to the pain clinic due to allodynia on the tongue and gingival, and hypesthesia was also present on the left half of the face. Trigeminal nerve block with dehydrogenated alcohol and stellate ganglion block with 1% mepivacaine were performed and oral medication with diphenylhydantoin was started. The symptoms were alleviated after nerve block and oral medication. Dizziness, blurred vision and ataxia then developed from the 13th hospital day. We considered the symptoms as a side effect of diphenylhydantoin and we reduced the dose of diphenylhydantoin. However, the symptoms grew worse. Another brain MRI showed a slight increase of the tumor size and a mass effect with displacement of the adjacent organs, and hydrocephalus was also noted. This case shows the importance of considering the secondary symptoms that are due to brain tumor while treating trigeminal neuralgia. The changes of the brain tumors should also be considered along with the presence of new side effects.

• Journal of Pharmaceutical Investigation
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• 제37권2호
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• pp.79-84
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• 2007

This study was aimed to establish analytical method of Bi to develop a guideline of the bioequivalence test of tripotassium dicitrato bismuthate (TDB). For this purpose, a simple, specific and sensitive inductively coupled plasma-mass spectrometry (ICP/MS) method were developed and validated in human plasma. Various concentrations of bismuth standard solution (0-25ng/mL) were prepared with distilled water and human blank plasma. To 10mL of the volumetric flasks, 2mL of blank plasma was added with 8ml of distilled water. Bi standard solution was added to prepare the calibration samples and injected into ICP-MS. The plasma samples obtained from volunteers given 3 tablets of bismuth (total 900mg as TDB) were analyzed as described above. As a result, the coefficients of variation were <20% in quantitation limit (0.2 ng/mL) and <15% at the rest of concentrations. The stability test by repeated freezing-thawing cycles showed that the samples were stable only for 24hr. The stability tested for samples with a short-term period of storage at room temperature and pre-treatment prior to the analysis showed very stable over 24hr. In 8 healthy Korean subjects received Denol tablets at the dose of 900mg bismuth, AUC, $C_{max},\;T_{max}$ and half-life $(t_{1/2})$ were determined to be $198.33{\pm}173.78 ng{\cdot}hr/mL,\;64.48{\pm}27.06 ng/mL,\;0.52{\pm}0.21 hr,\;and\;5.15{\pm}2.67 hr$, respectively, from the plasma bismuth concentration-time curves. In conclusion, the method was suitable for the determination of bismuth in human plasma samples and could be applied to bioequivalence test of bismuth tablet.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.209-213
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• 2002

Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration $(C_{max})$ and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.

• 농약과학회지
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• 제4권4호
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• pp.48-55
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• 2000

도시민과 농민의 농약 독성에 대한 인지도를 설문을 통하여 조사한 결과는 다음과 같다. 응답 도시민의 60%는 우리나라의 식량 자급률이 50% 이상 되는 것으로 생각하고 있었다. 또 농업에서 농약이 필요하다고 답한 도시민은 응답자의 60% 정도로 나타났다. 도시민은 농민이 농약을 과다하게 사용하고 있으며 또 농작물에 농약이 잔류된다고 생각하고 있었다. 잔류농약이 만성독성을 유발시키거나 암의 원인이 된다고 대답하였다. 상당수의 도시민은 유기 농산물을 선호하는 편이었으나 완전한 무농약 재배라고는 믿지 않았다. 농민에 대한 설문 조사 결과 농민은 농약이 농업에 절대적으로 필요한 것으로 나타났다. 응답 농민의 반 정도는 추천 사용량의 2배 정도의 농도로 농약을 처리하는 것으로 나타났다. 농민들 역시 농작물에 농약이 어느 정도는 잔류되는 것으로 생각하고 있으나 농약이 잔류허용량 이상으로 잔류된 농작물을 유통시켰을 때 처벌되는 것에 대하여는 모르고 있는 것으로 나타났다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10057-10059
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• 2015

Positron emission tomography (PET) as the functional component of current hybrid imaging (like PET/CT or PET/MRI) seems to dominate the horizon of medical imaging in coming decades. $^{18}$Flourodeoxyglucose ($^{18}FDG$) is the most commonly used probe in oncology and also in cardiology and neurology around the globe. However, the major capital cost and exorbitant running expenditure of low to medium energy cyclotrons (about 20 MeV) and radiochemistry units are the seminal reasons of low number of cyclotrons but mushroom growth pattern of PET scanners. This fact and longer half-life of $^{18}F$ (110 minutes) have paved the path of a centralized model in which $^{18}FDG$ is produced by commercial PET radiopharmacies and the finished product (multi-dose vial with tungsten shielding) is dispensed to customers having only PET scanners. This indeed reduced the cost but has limitations of dependence upon timely arrival of daily shipments as delay caused by any reason results in cancellation or rescheduling of the PET procedures. In recent years, industry and academia have taken a step forward by producing low energy, table top cyclotrons with compact and automated radiochemistry units (Lab-on-Chip). This decentralized strategy enables the users to produce on-demand doses of PET probe themselves at reasonably low cost using an automated and user-friendly technology. This technological development would indeed provide a real impetus to the availability of complete set up of PET based molecular imaging at an affordable cost to the developing countries.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.383-388
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• 2005

A simple and specific method for determination of methyltestosterone (MT) has been established by a gas chromatography/mass selective detector and applied in plasma of healthy male volunteers received a single oral dose of 50 mg MT $(Testo^{TM}\;tablets,\;25\;mg)$ for bioavailability test. This method involves using liquid-liquid extraction of the sample with diethyl ether and derivatization with MSTFA. MT showed good resolution in this condition. The detection limit of quantitation was 5 ng/ml. A good linearity (r>0.996) was obtained at the range of 5-250 ng/ml of MT. Intra-day precision and accuracy were 2.76-12.56% and 0.39-8.01 %, and inter-day precision and accuracy were 2.29-17.69% and 0.42-7.99%, respectively. The established method was applied on bioavailability test of MT in human volunteers. The value of $AUC_{0\;to\;last}$ to last was $264.5{\pm}123.9\;ng{\cdot}hr/ml$ and that of $AUC_{0\;to\;inf}$ was determined to be $275.2{\pm}126.5\;ng{\cdot}hr/ml$. The values of $C_{max}$ and $T_{max}$ were $95.9{\pm}67.1\;ng/ml$ and $1.13{\pm}0.9\;hr$, respectively. The mean elimination half-life $(t_{1/2})$ was $4.4{\pm}0.9\;hr$. This analytical method is suitable and useful for the pharmacokinetics and bioequivalence studies of MT.