• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.289-294
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• 1998

Bioequivalence of two aceclofenac tablets, the $Airtal^{TM}$ (Daewoong Pharmaceutical Co., Ltd.) and the $Senital^{TM}$ (Hana Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age $20{\sim}29$ years old) were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of aceclofenac was orally administered, blood was taken at predetermined time intervals and the concentration of aceclofenac in plasma was determined with an HPLC method using UV detector. The pharmacokinetic parameters ($C_{max}$, $T_{max}$ and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in $C_{max}$, $T_{max}$ and $AUC_t$ between two tablets were 3.69%, 2.44% and 0.51%, respectively. The powers $(1-{\beta})$ for $C_{max}$, $T_{max}$ and $AUC_t$ were 87.85%, 98.70% and more than 99%, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Senital^{TM}$ tablet is bioequivalent to $Airtal^{TM}$ tablet.

• 약학회지
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• 제42권5호
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• pp.513-518
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• 1998

Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.499-504
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• 2004

Paroxetine, a potent and selective serotonine reuptake inhibitor, has been used for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. The bioequivalence of two paroxetine preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Samchully Paroxetine $tablet^{\circledR}$ made by Samchully Pharm. Co. and the reference product was Seroxat $tablet^{\circledR}$ made by GlaxoSmithKline. Twenty healthy male subjects, $22.4{\pm}2.6$ years old and $63.8{\pm}4.2\;kg$, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 20 mg paroxetine was orally administered, blood was taken at predetermined time intervals and the concentration of paroxetine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.84-log 1.16 and log 0.85-log 1.14, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Samchully Paroxetine tablet is bioequivalent to Seroxat tablet.

• 대한핵의학회지
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• 제36권2호
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• pp.121-132
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• 2002

목적: Taxol(Paclitaxel)은 난소암과 유방암의 치료제로 사용되고 있으며, 치료시 적절한 체내 혈중농도를 유지함으로서 치료효과를 극대화하기 위해서는 taxol의 혈중농도를 측정하는 것이 필요하다. 본 실험에서는 taxol의 혈중농도를 측정할 수 있는 방사면역측정시스템에 표지항원으로 사용할 수 있는 taxol 유도체의 방사성표지화합물을 합성하고, 이를 이용하여 방사면역측정법을 시행할 수 있는지의 여부를 확인하고자 하였다. 대상 및 방법: Taxol과 succinic anhydride를 무수 pyridine을 용매로 하여 반응시켜 hemisuccinyltaxol을 합성하고, 합성된 hemisuccinyltaxol과 tyramine을 isobutylchloroformate를 coupling agent로 사용하여 tyraminehemisuccinyltaxol을 합성하고 HPLC로 분리 정제 하였다. 산화제인 Chloramine-T($5.25mg/ml,\;10{\mu}{\ell}$)를 사용하여 tyraminehemisuccinyltaxol($4mg/ml,\;30{\mu}{\ell}$)에 $^{125}I(1\;mCi)$를 방사성요오드화하고 HPLC를 이용하여 표지수율을 산정하였다. 정제된 tyraminehenisuccinyltaxol과 $^{125}I-iodotyraminehemisuccinyltaxol$을 80% acetonitrile 수용액에 녹여 $4^{\circ}C$와 $37^{\circ}C$로 보관하면서, 각 시간대별로 화학적 순도와 방사 화학적 순도를 결정하여 그 안정도를 HPLC를 이용하여 확인하였다. $[^{125}I]Iodotyraminehemisuccinyltaxol$를 방사성표지항원으로 사용하여 taxol에 대한 단클론항체(3G5A7)의 역가를 검정하였으며, $0{\sim}100nM$ 농도범위에서 taxol 농도의 증가에 따른 표준투여응답곡선을 작성하였다. 결과: Hemisuccinyltaxol은 79.9%의 수율로 합성되었으며, tyraminehemisuccinyltaxol의 합성수율은 19.5%였다. $^{125}I-iodotyraminehemisuccinyltaxol$의 표자수율은 93%이었다. tyraminehemisuccinyltaxol은 7일까지도 96.5% 이상의 순도를 보여 비교적 안정함을 확인하였으며, $^{125}I-iodotyraminehemisuccinyltaxol$은 3일까지는 93.4% 이상으로 안정하였고 또한 7일 경과시에는 86.1% 이상의 순도를 보였다. taxol에 대한 단클론항체(3G5A7)의 역가를 검정하여 1:256의 역가를 나타냄을 확인하였으며, taxol 농도에 따른 표준투여응답곡선은 taxol과 방사표지 taxol 유도체간에 경쟁적으로 사용되어 직선성 (R2=0.971)을 나타내었다. 결론: taxol의 경쟁적 방사면역측정법의 방사성 추적자로서 방사성표지 taxol 유도체인 $^{125}I-iodotyraminehemisuccinyltaxol$을 이용한 방법이 유용함을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제15권12호
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• pp.1714-1718
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• 2002

Twelve prepubertal Karan Fries heifers (15 months, $167.7{\pm}13.5kg$) were divided into two equal groups. Group 1 was fed as per NRC requirements and group 2 was fed 20% more protein than group 1 heifers. The experimental feeding was continued until the onset of puberty in both the groups. Blood samples were collected at fortnightly intervals and analyzed for amino acids using HPLC. Group 1 and 2 heifers required $178.6{\pm}33.8$ and $152.8{\pm}33.2$ days of experimental feeding to exhibit first estrus resulting in total age at puberty as $639.4{\pm}27.3$ and $618.6{\pm}24.6$ days in the two groups respectively. The concentration of total amino acids averaged 4.40 and 4.89 mmol/l and those of non-essential amino acids (NEAA) was 2.32 and 2.49 mmol/l in groups 1 and 2, respectively. The concentration of plasma essential amino acids i.e. histidine, threonine, valine, methionine, isoleucine, leucine and phenylalanine were higher (p<0.01) in group 2 than group 1. Plasma concentration of large neutral amino acids (LNAA) was significantly higher in group 2 (1.28 mmol/l) than in group 1 (1.12 mmol/l). Increased levels of leucine, isoleucine and valine are implicated in increased follicular growth and development in prepubertal heifers and resulted in a 26 day earlier attainment of puberty by 26 days in an experimental period of six months in group 2 heifers. Increased concentrations of aspartate and tyrosine in group 2 heifers might be associated with the release of GnRH from the hypothalamus influencing LH release from anterior pituitary in such animals. It is therefore evident that increased availability of certain amino acids in heifers fed high protein diet might have led to early onset of puberty.

• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.349-353
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• 1999

A novel polymeric tablet of tinidazole (TD) was formulated to treat Helicobacter pylori and Giardia lambria more efficiently with reduced hepatotoxicity by controlling the release of TD after oral administration. TD tablets containing various concentrations of either xanthan gum (XG, viscosity enhancer) and/or polycarbophil (PC, mucoadhesive) were prepared by the wet granulation method. In vitro release of TD into pH 2.0 and pH 5.0 buffer solutions was observed at 37°C by using an USP dissolution tester and an UV (313 nm) spectrophotometer. In vivo absorption of TD tablets was investigated in rabbits by measuring the blood concentration of TD after oral administration using a HPLC. Compared to a commercial TD tablet, in vitro release of TD in both pH 2.0 and pH 5.0 buffer solutions significantly decreased as the concentration: of XG or PC in the tablet increased up to 30%. However, when XG and PC was added in combination, TD was completely released in a pH 5.0 buffer solution within 8 hours, whereas the release of TD in pH 2.0 buffer solution significantly decreased. TD in a commercial tablet was rapidly absorbed after oral administration in rabbits. After oral administration of the polymeric tablets that contain both XG and PC, plasma concentration of TD dramatically decreased. Since the oral absorption of TD significantly decreased by the addition of XG and PC in the tablets while TD completely released in a pH 5.0 buffer solution, it was speculated that more TD was retained in the gastrointestinal tract. Thus, it was possible to control the release of TD by changing the content of XG and/or PC in the tablet, thereby manipulating the release rate and the gastrointestinal retention of TD after oral administration in rabbits.

• Journal of Preventive Medicine and Public Health
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• 제33권1호
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• pp.45-50
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• 2000

Objectives : This study was undertaken to evaluate correlation between the levels of hippuric acid in blood plasma (HAP) and those of toluene concentration in the workplace air. Methods : Study subjects were composed of two groups; 21 workers who were occupationally exposed to toluene and 25 rural-area residents who were not exposed to any known occupational toluene source, as an exposed group and a reference group, respectively. Mean age and work duration of the exposed was 42 years and five years, respectively. Mean age of the reference was 42 years. To determine toluene concentrations in the workplace air, air sampling has been conducted for more than six hours using a personal sampler, and analyzed by a gas chromatography-flame ionization detector. Concentrations of hippuric acid in biological samples were determined by a high performance liquid chromatography-ultraviolet detector. Results : Geometric mean(geometric standard deviation) of HAP and hippuric acid in urine(HAU) for the exposed was 1.39(2.21) mg/L and 2.77(1.46) g/L, respectively, which were significantly different from those of the reference [HAP, 9.45(2.94); HAU, 0.37(0.45)]. Teluene concentration in the workplace air was 86.92(range: $45.18\sim151.23$)ppm. The level of HAP or HAU was significantly correlated (r=0.70 and r=0.63, respectively) with that of toluene in the workplace air. The estimated regression equation was logHAP(mg/L)=-3.60+1.93 log(toluene, ppm) or logHAU(g/L)=-0.85+0.67 log(toluene, ppm). The magnitude of correlation was further enhanced when analyzing relationship between toluene concentrations lower than 100 ppm and its corresponding HAP levels. Conclusion : Overall, plasma hippuric acid levels were well correlated with toluene concentrations in the workplace air, and a statistically significant correlation was observed for the samples with toluene concentration lower than 100 ppm.

• Journal of Pharmaceutical Investigation
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• 제29권2호
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• pp.145-149
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• 1999

Bioequivalence of two cefixime capsules, test drug ($Cepirin^R$ capsule: Cheiljedang Corp.) and reference drug ($Suprax^R$ capsule: Dong A Pharm. Com.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered the drug orally at the dose of 400 mg as cefixime in a $2{\times}2$ crossover study. There was a 1-week washout period between the administrations. Blood samples were taken at predetermined time intervals for 12 hour and the plasma concentration of cefixime was determined with a HPLC method. $AUC_{0-12hr}$ (area under the plasma concentration-time curve form time zero to 12 hour), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentrationtime data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-12hr}$, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences of these parameters between the formulations were less than 20% (i.e., 8.62, 11.10 and 0.00% for $AUC_{0-12hr}$, $C_{max}$ and $T_{max}$,respectively). The powers $(1-{\beta})$ for $AUC_{0-12hr}$ $C_{max}$ and $T_{max}$ were over 0.9. Minimal detectable difference $({\Delta})$ at ${\alpha}=0.05$, $1-{\beta}=0.8$ were less than 20% (i.e., 12.84, 11.05 and 17.99% for $AUC_{0-12hr}$, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals $({\delta})$ for these parameters were also within ${\pm}20%$ (i.e., $-0.53{\le}{\delta}{\le}17.76$, $3.23{\le}{\delta}{\le}18.97$ and $-12.81{\le}{\delta}{\le}12.81$ for $AUC_{0-12hr}$, $C_{max}$ and $T_{max}$, respectively). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two formulations of cefixime were bioequivlent.

• 약학회지
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• 제50권1호
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• pp.8-14
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• 2006

A 1 : 1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a dose of 30 mg/kg ACF in rats. to analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the samples were linear over the concenration range of $0.05{\sim}200\;{\mu}g/ml$. The intra- and inter-day assay accuracies of this method were within ${\pm}15\%$ of norminal values and the precision did not exceed $15\%$ of relative standard diviation. The lower limits of quantitation were 50 ng/ml for both TRF and PRF. The distribution of TRF or PRF was determined by 48 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF. TRF and PRF were distributed as the following order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12 h after i.m. administration were not detected. The number of the platelets in the 1 ml of the blood was calculated to be $0.183{\times}10^8/ml$ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24 h after i.m. administration of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF.

• Archives of Pharmacal Research
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• 제20권5호
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• pp.480-485
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• 1997

The absorption profile of phenytoin Na emulsion were examined compared to that of phenytoin suspension after oral administration in the rat. The corn oil-in-water emulsion, particle size of $184{\pm}$57.8 nm, was prepared using a microfludizer, and phenytoin Na added by shaft homogenizer. The phenytoin emulsion or suspension, 100 mg/kg, were intubated intragastrically using oral dosing needle and blood samples were withdrawn via an indwelling cannula from the conscious rat. Plasma concentrations of phenytoin were measured with HPLC using phenacetin as an internal standard. The plasma concentration versus time data were fitted to a one compartment open model and the pharmacokinetic parameters were calculated using the computer program, Boomer. The phenytoin plasma concentrations from the emulsion at each observed time were about 1.5-2 times higher than those from the suspension, significantly at time of 5, 6 and 7 hr after administration. The absorption $(k_a)$ and elimination rate constant $(k_e)$ were not altered significantly, however the AUC increased from 65.6 to $106.7{\mu}ghr/ml$ after phenytoin suspension or emulsion oral administration, respectively. From an equilibrium dialysis study, the diffusion rate constant $(k_{IE})$ was considerably higher from the phenytoin Na emulsion $(0.0439 hr{-1})$ than phenytoin suspension $(0.0014 hr{-1})$.