• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.255-262
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• 2011

Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.370-378
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• 2005

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-${\alpha}$, IL-1${\beta}$ and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines' level and frequencies of detection were compared. The level of IL-1${\beta}$was not significant different in all groups. but the level of TNF-${\alpha}$, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p<0.01) and the level of TNF-a(p<0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p<0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson's correlation coefficient (r=0.833)(p<0.001). The results indicated that the TNF-${\alpha}$, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-${\alpha}$, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders.

• 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.26 no.1
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• pp.86-94
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• 1992

Quantitative analysis of gallbladder emptying is important in diagnosis of motility disorder of gallbladder and in studies of biliary physiology. However, the normal range of gallbladder ejection fraction (GBEF) has not been determined yet and the best method for stimulating the gallbladder to contract has not been elucidated adequately. The purpose of this study was to compare the gallbladder emptying effect of the fatty meal ingestion with that of the continuous infusion of cholecystokinin (CCK) and to establish the normal GBSF values of normal subjects. Quantitative hepatobiliary scan with $^{99m}Tc-DISIDA$ after a fatty meal was performed for 22 normal healthy volunteers. Among them, 10 subjects repeated the test with a fatty meal. Again, for 7 subjects quantitative heaptobiliary scan with an infusion of CCK (sincalide) at a rate of 20 ng/kg/hr for 45 minutes was performed repeatedly. The results were as follows. 1) With a fatty meal, the mean GBEF was $89.6{\pm}8.2%$ in 22 normal subjects, and there was no difference between subjects. 2) With a continuous infusion of CCK, the mean GBEF was $62.4{\pm}16.6%$ in 7 normal subjects, and there was a significant difference between subjects(p<0.05). 3) The reproducibility of GBEF by a fatty meal was significantly higher than by an infusion of CCK (p < 0.05). 4) The mean GBEF by a fatty meal was significantly higher than that by an infusion of CCK (p < 0.05). We concluded that a fatty meal is superior to a continuous infusion of CCK for inducing gall-bladder contraction because that induces more complete emptying and the response is more reproducible and constant.

• The Journal of Internal Korean Medicine
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• v.33 no.1
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• pp.14-25
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• 2012

Objectives : To observe physiological changes during clinical acupuncture treatment. Methods : We recruited 40 healthy volunteers who had experienced an acupuncture treatment at least once within the past three years. The experimental group was divided into four groups according to the needling site and frequency of electrical stimulation. Sites consisted of abdomen and legs. Frequencies consisted of 100 Hz and 2 Hz. The procedures of experimental treatment consisted of seven phases, Resting I phase (Resting I), Needle insertion phase (Insertion), Maintenance of needle insertion I phase (Maintain I), Electrical stimulation phase (ES), Maintenance of needle insertion II phase (Maintain II), Needle removal phase (Removal) and Resting II phase (Resting II). We measured the surface electromygraphy (SEMG) through an electrode on the frontalis muscle during all phases consecutively. Results : When SEMGs of all seven phases were analyzed, they significantly increased or decreased according to phases. SEMGs of Insertion, Maintain I, ES and Maintain II phase significantly increased more than RestingI in abdomen and legs groups. SEMGs of the abdomen group were measured as being $4.78{\pm}0.74{\mu}V$ on Resting I, $16.48{\pm}3.97{\mu}V$ on Insertion, $46.31{\pm}10.56{\mu}V$ on Maintain I, $45.88{\pm}9.72{\mu}V$ on ES, $45.56{\pm}9.69{\mu}V$ on Maintain II, $18.76{\pm}3.05{\mu}V$ on Removal, and $3.75{\pm}0.65{\mu}V$ on Resting II. SEMGs of the legs group were measured as being $3.34{\pm}0.35{\mu}V$ on Resting I, $12.11{\pm}1.76{\mu}V$ on Insertion, $36.74{\pm}6.99{\mu}V$ on Maintain I, $33.57{\pm}6.30{\mu}V$ on ES, $32.66{\pm}6.03{\mu}V$ on Maintain II, $14.08{\pm}2.15{\mu}V$ on Removal, and $2.88{\pm}0.32{\mu}V$ on Resting II. Conclusions : SEMG changed differently according to processes of acupuncture. Electrical stimulation showed different change of SEMG. Thus, acupuncture treatment may change the status of the autonomic nervous system.

• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.54-58
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• 2009

Background: Obstructive sleep apnea (OSA) is associated with several cardiovascular diseases. However, the mechanisms are not completely understood. The measure of common carotid artery intima-media thickness (IMT) has been extensively used as an early marker of atherosclerosis. The aim of this study was to test the hypothesis that early signs of atherosclerosis are present in patients with OSA and correlate with OSA severity Methods: Eleven male patients with OSA were studied by using full standard overnight polysomnography and high-definition echo-tracking device to measure intima-media thickness and carotid artery diameter. Eight healthy volunteers matched for age and sex were studied by portable respiratory monitoring device. All participants were free of hypertension, diabetes, and were not on any medications. Patients with OSA were naive to treatment. Results: All patients and normal controls were male. There was no significant difference of age between patients and controls ($48.4{\pm}8.85$ and $48.0{\pm}9.77$). Significant differences existed between control subjects and patients with mild to moderate and severe OSA (apnea-hypopnea index, $1.51{\pm}1.15$ and $38.51{\pm}19.13$ respectively) in intima-media thickness ($0.59{\pm}0.064$ and $0.93{\pm}0.16$; P=0.0023), and carotid diameter ($5.79{\pm}0.44$ and $6.47{\pm}0.51$; P=0.0227). Multivariate analyses showed that the apnea-hypopnea index correlated independently with intima-media thickness and carotid diameter (r=0.79, P=0.0008, and r=0.47, P=0.0482). Conclusions: Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis, which further supports the hypothesis that OSA plays an independent role in atherosclerosis progression.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.117-122
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• 2005

After establishing improved HPLC analytical method of cefaclor in human plasma samples, a bioavailability study of cefaclor capsules was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). The standard calibration curve using an HPLC with UV detector was constructed in a range of $0.0324{\sim}16\;{\mu}g/ml$. The 6% perchloric acid instead of 6% trichloroacetic acid was used to precipitate plasma protein. The HPLC chromatograms were precisely and accurately resolved when spiked with human plasma spiked with cefaclor and cephalexin (internal standard). Twenty healthy male Korean volunteers received two commercial cefaclor capsules, $Neocef^{\circledR}$ capsule (Jinyang Pharm. Co., Ltd) or $Ceclor^{\circledR}$ capsule (Lilly Korea. Co., Ltd.) at the 250 mg cefaclor in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of cefaclor were monitored for 8 hours after oral drug administration. $AUC_t$ the area under the plasma concentration-time curve from time zero to 8 hr (13 points), 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 $Neocef^{\circledR}/Ceclor^{\circledR}$ were $0.9049{\leq}{\delta}{\leq}1.226$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Neocef^{\circledR}/Ceclor^{\circledR}$ with respect to the extent of absorption.

• 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.

• The Korean Journal of Food And Nutrition
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• v.11 no.3
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• pp.303-311
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• 1998

This study was carried out to determine the blood glucose responses to 10 kinds of typical Korean domestic meals, 9 kinds of eating out meals and 5 kinds of diabetic meals recommended by hospitals. The levels of blood glucose were measured at 15, 30, 60, 90 and 120 minutes after taking 24 kinds of meals(500$\pm$10㎉) and 50g of glucose to healthy volunteers. The blood glucose response areas and glycemic index(GI) were calculated. There was no invariable tendency of blood glucose responses among diabetic meals, general domestic meals and eating out meals. As the units of grain groups were increased, the GI of meals was increase. When the units of grain groups are same, the side dishes also affected the blood glucose responses, however, it is yet unknown what kinds of food materials of side dishes affected the blood glucose responses. Noodles (Chinese style, kalgugsu(Korean home made) and ramen) lowered blood glucose responses compared to steamed rice. Mixing barley and brown rice with polished rich also lowered blood glucose responses, especially when the mixing ratio of them was over the 15%. The lowering efficiency of barely was greater than brown rice. More than three grain units of rice increased the blood glucose response. The GI was significantly correlated with left area ratio(LAR), right area ratio(RAR) and blood glucose levels at 15, 30, 60, 90 minutes. The RAR and blood glucose levels at 30 minutes profoundly affected the GI.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.303-308
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two talniflumate tablets, SOMALGEN tablet (Kun Wha Pharm. Co., Ltd., Seoul, Korea, reference drug) and FLUTAL tablet (Kukje Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the talniflumate dose of 740 mg in a $2{\pm}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of niflumic acid were monitored by an HPLC-UV for over a period of 14 hr after the administration. $AUC_t$(the area under the plasma concentration-time curve from time zero to 14 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 $AUC_t$, $C_{max}$ and untransformed $T_{max}$. 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 SOMALGEN/FLUTAL were $log0.8510{\sim}log1.0318$ and $log0.9264{\sim}log1.0607$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Taken together, our study demonstrated the bioequivalence of SOMALGEN and FLUTAL with respect to the rate and extent of absorption.