• YAKHAK HOEJI
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• v.53 no.5
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• pp.259-264
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• 2009

The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.252-257
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• 2010

The aim of this study was to investigate the effect of resveratrol on the pharmacokinetics of nifedipine in rats. The pharmacokinetic parameters of nifedipine were measured after the oral administration of nifenipine (6 mg/kg) in the presence or absence of resveratrol (0.5, 2.5 and 10 mg/kg, respectively). The effect of resveratrol on the P-glycoprotein (Pgp), CYP 3A4 activity was also evaluated. Resveratrol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 0.94 ${\mu}M$. In addition, resveratrol significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared to the control groups, the presence of 2.5 mg/kg and 10 mg/kg of resveratrol significantly (p<0.05, p<0.01) increased the area under the plasma concentrationtime curve (AUC) of nifedipine by 49~75%, and the peak concentration ($C_{max}$) of nifedipine by 48~66%. The absolute bioavailability (AB%) of nifedipine was significantly (p<0.05) increased by 22.9-34.8% compared to the control (19.8%). The terminal half-life ($T_{1/2}$) of nifedipine was significantly (p<0.05) increased compared to the control. While there was no significant change in the time to reach the peak plasma concentration ($T_{max}$) of nifedipine in the presence of resveratrol. It might be suggested that resveratrol altered disposition of nifedipine by inhibition of both the CYP3A and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of resveratrol significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of resveratrol or resveratrol-containing dietary supplenment with nifedipine should require close monitoring for potential drug interation.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.291-296
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• 2010

This study was to investigate the effect of baicalein, an antioxidant, on the bioavailability of nicardipine after orally or intravenously administered nicardipine in rats. Nicardipine was administered orally (12 mg/kg) or intravenously (4 mg/kg) with or without orally administered baicalein (0.4, 2 or 10 mg/kg) to rats. In the inhibitory effect of baicalein on CYP3A4 activity, baicalein inhibited CYP3A4 activity with $IC_{50}$ values of 9.2 ${\mu}M$. The cell-based P-gp activity test using rhodamine-123 also showed that baicalein (30-10 ${\mu}M$, p<0.01) significantly inhibited P-gp activity. Compared with the control group (given nicardipine alone), the area under the plasma concentration-time curve (AUC) was significantly (2 mg/kg, P<0.05; 10 mg/kg, P<0.01) increased by 25.9-60.0%, and the peak concentration ($C_{max}$) was significantly (10 mg/kg, P<0.01) increased by 40.0% in the presence of baicalein after orally administration of nicardipine. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.26- to 1.60-fold and the absolute bioavailability (A.B.) was significantly (2 mg/kg, P<0.05; 10 mg/kg, P<0.01) increased by 26.0-59.9%. Compared to the i.v. control, baicalein did not significantly change pharmacokinetic parameters of nicardipine in i.v. administration. Accordingly, the enhanced oral bioavailability of nicardipine might be mainly due to increased intestinal absorption caused by P-gp inhibition rather than to reduced elimination of nicardipine by baicalein. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the small intestine via the inhibition of P-gp and reduced first-pass metabolism of nicardipine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by baicalein. Based on these results, nicardipine dosage should be adjusted when given concomitantly with baicalein.

• Korean Journal of Applied Biomechanics
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• v.17 no.1
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• pp.1-8
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• 2007

Ground reaction force (GRF) measures are one of the most commonly used in biomechanical study. GRF system is very useful educational tool to explain and demonstrate the Newton's law of universal gravitation and laws of motion as well. However, accuracy, intra- and inter- force platform measures' consistency, reliability, noise, and the effect of platform mounting to GRF measures were not clearly viewed. The aim of this study was to examine the above. GRFs of a plastic dummy and two subjects' quiet upright standing were collected at four university laboratories eight force platforms. The types of platforms, analysis programs, and platform set-up were various. Three 100s-trials were conducted with sampling frequency of 100 Hz. First two trials' vertical component of GRFs, Fz, and CoP sway ranges of mid-60s-portion of 100s trials were analyzed by the paired t-tests and one-way ANOVA. Six of eight platforms' 1st and 2nd trial dummy Fz were statistically different (p<.05) and all platforms ICC were poor (<.28). Fz of the two platforms in every four laboratories were statistically different (p<.05). There were white noises and/or very distinctive noises at specific frequency ranges in all Fz measures. 5 Hz low-pass filtering made clear the Fz differences. CoP ranges of dummy were less than 0.5 cm and the best was 0.02 cm. This CoP range finding agrees with previous results suggests the importance of force platform mounting and A/D card resolution.

• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• The Journal of the Acoustical Society of Korea
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• v.16 no.4
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• pp.57-63
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• 1997

In this paper, we study the efficient feature vector extraction method and front-end processing to improve the performance of the speech recognition system using KT(Korea Telecommunication) database collected through various telephone channels. First of all, we compare the recognition performances of the feature vectors known to be robust to noise and environmental variation and verify the performance enhancement of the recognition system using weighted cepstral distance measure methods. The experiment result shows that the recognition rate is increasedby using both PLP(Perceptual Linear Prediction) and MFCC(Mel Frequency Cepstral Coefficient) in comparison with LPC cepstrum used in KT recognition system. In cepstral distance measure, the weighted cepstral distance measure functions such as RPS(Root Power Sums) and BPL(Band-Pass Lifter) help the recognition enhancement. The application of the spectral subtraction method decrease the recognition rate because of the effect of distortion. However, RASTA(RelAtive SpecTrAl) processing, CMS(Cepstral Mean Subtraction) and SBR(Signal Bias Removal) enhance the recognition performance. Especially, the CMS method is simple but shows high recognition enhancement. Finally, the performances of the modified methods for the real-time implementation of CMS are compared and the improved method is suggested to prevent the performance degradation.

• Journal of Korea Society of Industrial Information Systems
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• v.6 no.3
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• pp.107-114
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• 2001

This paper describes Connected Digit Recognition with Considering Acoustic Feature in Korea. The recognition rate of connected digit is usually lower than word recognition. Therefore, speech feature parameter and acoustic feature are employed to make robust model for digit, and we could confirm the effect of Considering. Acoustic Feature throughout the experience of recognition. We used KLE 4 connected digit as database and 19 continuous distributed HMM as PLUs(Phoneme Like Units) using phonetical rules. For recognition experience, we have tested two cases. The first case, we used usual method like using Mel-Cepstrum and Regressive Coefficient for constructing phoneme model. The second case, we used expanded feature parameter and acoustic feature for constructing phoneme model. In both case, we employed OPDP(One Pass Dynamic Programming) and FSA(Finite State Automata) for recognition tests. When appling FSN for recognition, we applied various acoustic features. As the result, we could get 55.4% recognition rate for Mel-Cepstrum, and 67.4% for Mel-Cepstrum and Regressive Coefficient. Also, we could get 74.3% recognition rate for expanded feature parameter, and 75.4% for applying acoustic feature. Since, the case of applying acoustic feature got better result than former method, we could make certain that suggested method is effective for connected digit recognition in korean.

• Korean Journal of Social Welfare
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• v.66 no.2
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• pp.51-74
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• 2014

This study aimed to examine a multiple mediator model in which stresses affect self-criticism. The self-criticism, in turn seemed to affect the feelings of loneliness, and this had an effect on over 65 years living alone. Furthermore, whether social support had any moderating effects in the pathway from the loneliness to suicidal ideation on our pass model were also investigated. Data were collected from 572 samples of persons 65 years of age and older living alone in Seoul. For the analyses of the mediating effects and moderating effects, structural equation modeling was used. The results were as follows. First, the pass model was identified to fit the observed data. This mean that self-criticism increased as stress rises, the increased levels of self-criticism increased loneliness, and the increased levels of loneliness increased the levels of suicidal ideation. Second, social support moderated the relation between loneliness and suicidal ideation on our model. These results suggested that interventions which deal with loneliness and suicidal ideation were needed, in order to reduce suicidal ideation caused by the stress. These imply, additionally, that when social workers try to reduce the suicidal ideation, they should consider the levels of social support at work as influences.

• THE INTERNATIONAL COMMERCE & LAW REVIEW
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• v.16
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• pp.83-114
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• 2001

This paper is focussed on the main features and problems of SGA amendment. main features and problems are as below. First, SGA section 14 uses a new term, that of "satisfactory quality", which is defined in a somewhat circular way and introduces some guidelines in order to solve other problems perceived as arising under the "merchantable quality". The change was largely to assist in the better resolution of consumer disputes and not necessary for commercial disputes because the change involves the substitution of a phrase which meant something but was inappropriate to commercial disputes. As with the definition of "merchantable quality", a court can take the new formulation as an invitation to start afresh; or it can refer to the previous case law. Second, before the SGA amendment, a contract for the sale of undifferentiated part of a bulk shipped or to be shipped on a named ship was a contract for the sale of unascertained goods. So the effect was that property could not pass to the buyer, even though he had paid the price in full, before the goods become ascertained. The main object of the SGA amendment was to improve the buyer's position where he had paid for a specified quantity of goods forming an undifferentiated part of an identified bulk and the seller then became insolvent before the goods for which the buyer had paid were ascertained. The improvement was achieved by making section 16 of the SGA 1979 subject to a new section 20A and includig section 20B, under which a buyer of a specified quantity bulk can acquire a proprietary interest in the bulk. This proprietary solution still has some problems in international sale of goods. Therefore, it would be more appropriated SGA should settle disputes between parties through payment, passing of risk, delivery of goods and/or documents etc. instead of property rights like UCC.