• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.255-261
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• 2007

A bioequivalence study of $Nimegen^{TM}$ soft capsule (Medica Korea Pharma. Co., Ltd.) to $RoAccutane^{(R)}$ soft capsule (Roche Korea Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty healthy male Korean volunteers received each medicine at the isotretinoin dose of 60 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of isotretinoin were monitored by a high performance liquid chromatography (HPLC) for over a period of 48 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48 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 $Nimegen^{TM}/RoAccutane^{(R)}$ were $log0.860{\sim}log0.98\;and\;log0.85{\sim}log1.00$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Nimegen^{TM}\;and\;RoAccutane^{(R)}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.209-214
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• 2004

A bioequivalence study of $Roxithrin^{TM}$ tablet (Kukje Pharma. Ind. Co., Ltd.) to $Rulid^{TM}$ tablet (Han Dok Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the roxithromycin dose of 300 mg in a $2{\times}2$ crossover study. There was a one-week wash-out period between the doses. Plasma concentrations of roxithromycin were monitored by a high-performance liquid chromatography 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 cross-over design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Roxithrin^{TM}/Rulid^{TM}$ were 1.00 - 1.13 and 0.98 - 1.10, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25. Thus, our study demonstrated the bioequivalence of $Roxithrin^{TM}$ and $Rulid^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.165-177
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• 1993

The relationship between the plasma haloperidol (HP) concentration and clinical response, and the effects of its active metabolite, reduced haloperidol (RH) on clinical response of HP were investigated in schizophrenic patients. In clinical study I, with 17 schizophrenic patients (male 8, fermale 9) who were administered with three different fixed doses of HP (15, 30 and 50 mg/day) for 3 weeks, the concentrations of HP and RH in plasma and blood and clinical response had been checked before and every week during the study. The clinical response was evaluated by the method of brief psychiatric rating scale (BPRS), and relative improvement of clinical response based on baseline BPRS (before drug treatment) was calculated. The concentrations of HP and RH in plasma and blood were assayed by HPLC. In clinical study II, the plasma RH/HP concentration ratios were checked in 11 patients who were administered with high doses of HP, over 60 mg a day, because of the poor clinical response at usual doses of HP. Plasma HP concentration and relative improvement of BPRS at 3 week in schizophrenic patients showed a 'curvilinear' relationship, and the clinical response was improved relatively over 50% based on the baseline BPRS in the range of $5{\sim}57\;ng/ml $ of HP in plasma. Also, the plasma RH concentrations were increased nonlinearly as the plasma HP concentration increased, and in high plasma HP concentration, over 30 ng/mI, clinical response gradually decreased, while the plasma RH/HP concentration ratio increased nonlinearly. Blood partition coefficients of HP and RH were not changed according to daily HP dose and duration of drug therapy. From these results, it is noted that the higher plasma RH/HP concentration ratio, resulted from the accumulation of RH as HP concentration increased, might explain the 'curvilinear' decrease of HP clinical response.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.265-269
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• 2002

The purpose of this study was to report the pharmacokinetic changes of cyclosporine after oral administration of cyclosporine, 10 mg/kg, in rabbits coadministered or pretreated twice per day for 3 days with nimodipine, dose of 5 mg/kg. The area under the plasma concentration-time curve (AUC) of cyclosporine was significantly higher in rabbits pretreated with nimodipine than that in control rabbits (p＜0.01), showing about 149％ increased relative bioavailability. The peak plasma concentration (C$_{max}$), elimination half-life (t$_{1}$2/) and MRT of cyclosporine were increased significantly (p＜0.05) in rabbits pretreated with nimodipine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant and total body clearance by pretreated with nimodipine. The effects of nimodipine on the pharmacokinetics of oral cyclosporine were more considerable in rabbits pretreated with nimodipine compared with those in control rabbits. The results suggest that the dosage of cyclosporine should be adjusted when the drug would be coadministered chronically with nimodipine in a clinical situation.n.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.273-278
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• 2005

Nicotine transdermal therapeutic systems $(TTS_S)$ have been regarded as an effective mean to aid smoking cessation. However, most of nicotine $TTS_S$ in the market have some problems such as unpleasant side effects and skin irritation due to the excess amount of the drug permeated and the properties of the additives employed. In order to solve these problems, new nicotine $TTS_S$ were formulated using biocompatible additives. The optimized formula of the drug layer consisted of nicotine, propylene glycol and poloxamer 188 at the ratio of 1.2: 17.0: 2.0. The drug layer had the sickness of $1,250\;{\mu}m$, the pH of 8.12. The skin permeation rate of nicotine from optimized nicotine patch (NP) was $21.5\;{\mu}g/cm^2/h$. Transdermal administration of nicotine patch has been carried out for the determination of pharmacokinetic parameters in rats. Steady-state plasma concentration of nicotine following transdermal application of NP (area of patch = $15\;cm^2$) on the dorsal skin of rats was 143.2 ng/ml and AUC for 24 hrs was 3,022 ng h/ml. In case of $EXODUS^{\circledR}$ and Nicotinell $TTS^{\circledR}$, the steady-state plasma concentration of nicotine and ACU for 24 hrs were 428.9 ng/ml, $9,121\;ng{\cdot}hr/ml$ and 155.3 ng/ml, $3,152\;ng{\cdot}h/ml$, respectively. NP showed the experimental plasma nicotine concentration profile was very similar to the simulated one and had an appropriate skin permeation rate and a steady-state concentration of nicotine, which can show therapeutic blood levels of the drug for 24 hrs without severe side effects.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.64.1-64.9
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• 2022

Background: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. Objectives: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. Methods: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (C_max), time to reach maximum plasma concentration (t_max), area under the concentration-time curve values (AUC_0-21d), half-life (t_1/2), and other pharmacokinetic parameters were calculated. Results: Although the highest maximum plasma concentration (C_max) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the C_max, t_max, t_1/2, MRT_{0-inf_obs}, Vz/F_obs, and Cl/F_{_obs} parameters between the experimental groups. Conclusions: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.135-142
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• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom 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 Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.193-199
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• 2006

A bioequivalence study of $Sudo^{TM}$ Ranitidine HCI tablet (Sudo Pharma. Ind. Co., Ltd.) to $Curan^{TM}$ tablet (Il Dong Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the ranitidine hydrochloride dose of 150 mg in a 2x2 crossover study. There was a one week wash-out period between the doses. Plasma concentrations of ranitidine were monitored by a high-turbulent liquid chromatography (HTLC) for over a period of 12 hours after drug 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 far 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 $Sudo^{TM}$ Ranitidine $HCl/Curan^{TM}$ were 0.92-1.00 and 0.90-1.03, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Sudo^{TM}$ Ranitidine HCI and $Curan^{TM}$ with respect to the rate and extent of absorption.

• 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.