• 한국임상약학회지
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• 제8권2호
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• pp.101-106
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• 1998

A bioequivalence study of the Kerola tablets (Dongkwang Pharmaceutical Co., Korea) to the Tarasyn tablets (Roche Co., Korea), formulations of ketorolac trometamine(KTR), was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 10 mg as KTR in a $2\times2$ crossover study. There was a 1-week washout period between the dose. Plasma concentrations of KTR were monitored by an HPLC method for over a period of 12 hr after each administration. AUC (area under the plasma concentration-time curve) was calculated by the linear trapezoidal method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}\;and\;T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than $20\%$ (i.e., 2.31, 8.19 and $0\%$ for AUC, $C_{max}\;and\;T_{max}$, respectively). Minimum detectable differences $(\%)\;at\;\alpha=0.1\;and\;1-\beta=0.8$ were all less than $20\%$ difference in these parameters between the formulations were all over 0.8. The $90\%$ confidence intervals for these parameters were also within $20\%$. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the 2 formulations of KTR are bioequivalent and, thus, may be prescribed interchangeably.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.901-905
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• 2004

A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric(HILIC-MS/MS) method for the determination of tiapride in human plasma was developed. Tiapride and internal standard, metoclopramide were extracted from human plasma with dichloromethane at basic pH and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium formate (190 mM, pH 3.0) (94：6, v/v). The ana-Iytes were detected using an electrospray ionization tandem mass spectrometry in the multi-ple-reaction-monitoring mode. The standard curve was linear (r＝0.999) over the concentration range of 1.00-200 ng/mL. The coefficient of variation and relative error for intra- and inter-assay at three QC levels were 6.4∼8.8％ and -2.0∼3.6％, respectively. The recoveries of tiapride ranged from 96.3 to 97.4％, with that of metoclopramide (internal standard) being 94.2％. The lower limit of quantification for tiapride was 1.00 ng/mL using 1 00 $\mu$L of plasma sample.

• 약학회지
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• 제54권4호
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• pp.295-299
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• 2010

The aim of this study was to develop and validate for determination of alibendol in human plasma by HPLC method. After precipitation of 500 ${\mu}l$ plasma samples by 50% methanol 50 ${\mu}l$ and 60% perchloric acid 30 ${\mu}l$ and the supernatant 50 ${\mu}l$ was injected into HPLC. The assay was performed isocratically using 10 mM potassium phosphate (pH 3.0) and acetonitrile (80 : 20, v/v) as mobile phase. The $C_{18}$ column (particle size $3.5{\mu}m$, $4.6{\times}50$ mm, Zorbax Eclipse) was used as a solid phase. The mobile phase was delivered at a flow-rate of 1.7 ml/min, detection was by ultraviolet absorption at 232 nm and concentrations were calculated on the basis of peak areas. In these conditions, alibendol can be separated from ethylparaben, the internal standard, and endogenous substances. The retention times of alibendol and ethylparaben were just about 2.6 and 3.5 minutes, respectively. This rapid HPLC method was validated by examining the precision and accuracy for inter- and intra-day analysis. The standard curve was linear ($R^2$=1.0000) over the concentration range of 0.05~20 ${\mu}g$/ml. The inter-day relative standard deviation (R.S.D.) and accuracy were 0.2~12.2% and 94.4~101.2% (82.7% at the lower limit of quatitation). The intra-day R.S.D. and accuracy were 0.1~11.8% and 98.8~102.5%, respectively. The method was successfully applied to the determination of alibendol in plasma for a pharmacokinetic study.

• Mass Spectrometry Letters
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• 제4권3호
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• pp.55-58
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• 2013

Dioscin is a biologically active steroidal saponin with anticancer and hepatoprotective effects. A rapid, selective, and sensitive liquid chromatographic method with electrospray ionization tandem mass spectrometry was developed for the quantification of dioscin in rat plasma. Dioscin was extracted from rat plasma using ethyl acetate at acidic pH. The analytes were separated on a Halo C18 column using gradient elution of acetonitrile and 0.1% formic acid and detected by tandem mass spectrometry in selected reaction monitoring mode. The standard curve was linear ($r^2$ = 0.998) over the concentration range of 1-100 ng/mL. The lower limit of quantification was 1.0 ng/mL using 50 ${\mu}L$ of plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four QC levels were 1.3 to 8.0% and -5.4 to 10.0%, respectively. This method was applied successfully to the pharmacokinetic study of dioscin after oral administration of dioscin at a dose of 29.2 mg/kg in male Sprague-Dawley rats.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.99-104
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• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.241.2-241.2
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• 2003

The purpose of this study was to investigate the effect of quercetin(2.0, 10, 20 mg/kg; combined or pretreated) on the pharmacokinetic parameters and the bioavailability of diltiazem(15mg/kg) orally to rabbits. The plasma concentration of diltiazem pretreated with quercetin(pretreated group) were increased significantly (p<0.01) compared to that of control, but those of diltiazem combined with quercetin(combined group) were not affected. Area under the plasma concentration-time curve (AUC) of diltiazem pretreated with quercetin was significantly ( p<0.01) higher than that of control (omitted)

• 분석과학
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• 제21권1호
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• pp.34-40
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• 2008

LC-MS/MS를 이용하여 신속하고 정확한 혈장 중 레르카니디핀의 분석법을 개발하고 이 분석법에 대한 검증을 수행하였다. 혈장에 내부표준물질로 사용한 암로디핀을 첨가한 후 아세토니트릴로 단백질을 침전시키고, 그 상층액을 취하여 건조시킨 후 50 % 아세토니트릴로 재용해하여 LC-MS/MS로 분석하였다. MS/MS의 MRM (multiple reaction monitoring) 방법을 이용하여 혈장 중 레르카니디핀을 어떠한 분석의 방해물 없이 선택적으로 검출할 수 있었다. 레르카니디핀의 표준 검량선은 0.05-20 ng/mL의 농도 범위에서 우수한 직선성(r = 0.9994)을 보였으며, 일내, 일간 재현성은 변동계수 11.7% 이하, 정확성은 94.4-114.8%로 레르카니디핀의 약물동력학적 연구에 적용되기에 충분한 감도와 특이성, 직선성, 정밀성 및 정확성을 가지고 있음을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.355-360
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two cetirizine HCl tablets, Zyrtec tablet (UCB Pharm. Co., Ltd. Korea, reference product) and Zyrix tablet (Kukje Pharm. Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (diazepam), plasma samples were extracted using 1 mL of dichloromethane. Compounds extracted were analyzed by reverse-phase HPLC with ultra-violet detector. This method for determination cetirizine is proved accurate and reproducible with a limit of quantitation of 10 ng/mL in male plasma. Twenty-four healthy male Korean volunteers received each medicine at the cetirizine HCl dose of 10 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of cetirizine were monitored for over a period of 24 hr after the administration. AUC (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. Analysis of variance was carried out using logarithmically transformed AUC 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 for the log transformed data were acceptable range of log 0.8 to log 1.25 $(e.g.,\;log\;0.93-log\;1.08\;for\;AUC_{0-t},\;log\;0.91-log\;1.08\;for\;AUC_{0-{\infty}}\;and\;log\;1.01-log\;1.11\;for\;C_{max})$. The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that Zyrix tablet is bioequivalent to Zyrtec tablet.

• Archives of Pharmacal Research
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• 제17권5호
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• pp.364-370
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• 1994

A microscopic mass balance approach has been developed to estimate the extent and rate of absorption for camier-mediated comounds. For the case competitive inhibition in the presence of an inhibitor which shares the same camier, the fraction dose absorbed (F) and absorption rate constant ($K_a$) of a drug can be calculated from its concentration profile in the intestinal lumen. Absorption parameters obtained by single-pass perfusion experiments were used in the simultaion of the absorption of some aminopenicilins. Predicted fractions dose absorbed and absorption rate constants of ampicilin and amoxicilin were significantly reduced in the presence of a 6-times higher molar dose of cyclacilin. The drug-drug interactions on the competitive absroption of camier-mediated compounds were determined with regard to F and $K_a$. Predicted decreases in F for some aminopenicilins corrlated well with decrease in the urinary recovery in humans reported in the literature. Predicted decrease in the mean absorption rate constant ($\barK_a$) explain the delays in the time of peak plasma concentration ($T_{max}$) reported in humans.