• 한국임상약학회지
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• 제7권1호
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• pp.17-21
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• 1997

Cefaclor is a second generation cephalosporin antibiotic that shows a potent antibacterial activity against both Gram-positive and Gram-negative bacteria, when it is orally administered. Due to its patent expiration, a number of generic drugs have been marketed, but not yet elucidated to ensure therapeutic equivalence. In this study, cefaclor capsules manufactured by Chong Kun Dang were bioequivallently assessed by comparing with $Ceclor^{TM}$ introduced originally by Daewoong Lilly. A total of 16 healthy male volunteers were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of cefaclor in plasma were measured upto 6 hours following a single oral administration of two capsules (500 mg of cefaclor) by high-performance liquid chromatography with UV detection. Although the plasma concentration at 6 hours was not detected, the computed half-life of cefaclor was approximately 0.5 hours. The area under the concentration-vs-time curve from 0 to 4 hours $(AUC_{0-4h})$ was calculated by the trapezoidal summation method. The differences in mean values of $AUC_{0-4h}$, peak plasma concentration $(C_{max})$, and time to peak concentration $(T_{max})$ between the two products were $4.63\%,\;1.84\%,\;and\3.28\%$, respectively. The least significant differences at $\alpha4= 0.05 for $AUC_{0-4h},\;C_{max},\;and\;T_{max}\;were\;6,53\%,\;4.05\%,\;and\;6.47\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

• Journal of Pharmaceutical Investigation
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• 제33권3호
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• pp.201-208
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• 2003

Pharmacokinetics and oral bioavailability of levosulpiride was determined in Korean healthy male volunteers. Thirty subjects received a single oral dose (25 mg) of a tablet in a randomized $2{\times}2$ cross-over design. The plasma concentrations of levosulpiride were measured by HPLC and compared with those reported in the literature. Pharmacokinetic parameters for $Isomeric^{\circledR}$ tablet (levosulpiride 25 mg) were revealed as follows: $AUC_{inf}\;737.1{\pm}176.9\;ng{\cdot}hr/ml,\;C_{max}\;56.4{\pm}20.1\;ng/ml,\;T_{max}\;4.2{\pm}1.6\;hr,\;K_a\;1.00{\pm}1.09\;hr^{-1},\;K_{el}\;0.08{\pm}0.02\;hr^{-1},\;and\;t_{1/2}\;8.8{\pm}1.9\;hr$. The rate constant of the absorption phase was obtained based on the first-order kinetics. In the aspect of bioavailability, $Isomeric^{\circledR}$ tablet was bioequivalent to the other product $(Levopride^{\circledR}\;tablet)$ available in the Korea market. Intersubject variations and race differences were show in comparison with the published data in the literature, even though there was a linear relationship between dose ad extent of bioavailability.

• 대한핵의학회지
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• 제22권2호
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• pp.193-197
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• 1988

Measurement of gastric emptying rate has been performed by a variety of techniques. Nuclear medicine method is a major advance in the quantitative evaluation of gastric function and also of pharmacologic intervention. Normal gastric emptying rate was measured in 48 healthy volunteers using live chicken liver labeled with $^{99m}Tc-Tin$ Colloid as a solid phase marker. In vitro studies were performed to evaluate the labeling efficiency and stability in hydrochloric acid and in human gastric juice of intracellularly labeled chicken liver. Anterior image counts only were compared with the geometric mean of anterior and posterior counts in 12 healthy volunteers who were studied by both anterior count and posterior count. The results were as follows: 1) The labeling efficiency in gastric juice and hydrochloric acid were $95.5{\pm}1.23%,\;95.7{\pm}1.15%$, respectively. 2) Half gastric emptying time by anterior count only was $126{\pm}21$ minutes 3) Although standard deviation of geometric mean method was smaller than anterior count method, gastric emptying curves from both method were similar. In daily practice, anterior count method may be useful alternative to geometric mean method in evaluation of gastric emptying rate.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.118-122
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• 2007

This study was performed to evaluate the bioequivalency between the Osmetone$^{TM}$ Tablet (Myeongmoon Pharm. Co., Ltd.) as a test formulation and the Relafen$^{TM}$ Tablet (Handok Pharm. Co., Ltd.) as a reference formulation. Twenty-four healthy male volunteers were administered the formulations by the randomized Latin square crossover design, and the plasma samples were determined by a high performance liquid chromatography (HPLC) with Ultra-Violet (UV) detector. AUC$_t$, C$_{max}$ and T$_{max}$ were obtained from the time-plasma concentration curves, and log-transformed AUC$_t$ and C$_{max}$ and log-untransformed T$_{max}$ values for two formulations were compared by statistical tests and analysis of variation. AUC$_t$ was determined to be 897.8${\pm}$431.1 ug.hr/ml for the reference formulation and 902.3${\pm}$408.4 ug.hr/ml for the test formulation. The mean values of C$_{max}$ for the reference and test formulations were 24.2${\pm}$8.9 and 24.0${\pm}$9.5 ug/ml, respectively. The AUC$_t$ and C$_{max}$ ratios of the reference Relafen$^{TM}$ Tablet to the test Osmetone$^{TM}$ Tablet were +5.01% and -0.83%, respectively, showing that the mean differences were satisfied the acceptance criteria within 20%. The results from analysis of variance for logtransformed AUC$_t$ and C$_{max}$ indicated that sequence effects between groups were not exerted and 90% confidence limits of the mean differences for AUC$_t$ and C$_{max}$ were located in ranges from log 0.80 to log 1.25, satisfying the acceptance criteria of the KFDA bioequivalence. The Osmetone$^{TM}$ Tablet as the test formulation was considered to be bioequivalant to the Relafen$^{TM}$ Tablet used as its reference formulation, based on AUC$_t$ and C$_{max}$ values.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.343-348
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• 2008

The bioequivalence of two cyclosporine A (CyA) 100 mg soft capsules (Chong Kun Dang's $Cipol-N^{(R)}$ as the test drug; Korea Novartis' Sandimmun $Neoral^{(R)}$ as the reference drug) was assessed in healthy male Korean volunteers after oral administration of 200 mg CyA according to a randomized crossover design. The whole blood samples were analyzed for the determination of parent CyA in the blood by using a validated HPLC/diode array detector method. The mean $AUC_t$ values for reference and test products were $4095.3{\pm}1397.2$ and $3958.3{\pm}1138.2\;ng{\cdot}hr/mL$, respectively. The mean $C_{max}$ values were $1135.9{\pm}293.2\;ng/mL$ for the reference product, and $985.0{\pm}207.9\;ng/mL$ for the test product. $T_{max}$ was $1.6{\pm}0.4\;hr$ for the reference and $1.8{\pm}0.5\;hr$ for the test product. The differences of $AUC_t$, $C_{max}$ and $T_{max}$ were -3.35, -13.28 and +10.63%, respectively. The point estimates and 90% confidence intervals for $AUC_t$ and $C_{max}$ were 0.981 (0.9171 to 1.0514) and 0.876 (0.8229 to 0.9336), respectively. Based on the pharmacokinetic and statistical data, we conclude that these two products are bioequivalent and can be considered interchangeable in the medical practice.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.355-362
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• 2014

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

• 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.

• 한국한의학연구원논문집
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• 제6권1호
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• pp.69-80
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• 2000

Objectives : Assuming that the characteristic of meridian system has been similar to this of electric potentials in human body and that measurements of electric potential at well(井穴) and sea(合穴) points in branches of the twelves meridians will be representative of measurements of the twelve meridians, to measure the electric potentials in twenty healthy volunteers when they were sleeping or waking respectively, to do significance test for electric potential of meridian system between hand and foot meridian, yin and yang meridian, exterior and interior of the body, and among the five elements. Methods : When twenty healthy volunteers were sleeping, their electric potentials of well and sea points in branches of the twelve meridians were simultaneously measured by physiograph. After a minute we measured them again, totally 5 times. And then when they were waking, their electric potentials were measured 5 times by the above method. Results : Measurements were analyzed by statistical t-test, we obtained that the left side electric potential of hand or yin meridian was significantly different from that of foot or yang meridian both sleeping and waking. The right side of electric potential was the same result as the left side's. Most of the t-test was significant between exterior and interior of the body, and among the five elements. That meaned that it was partly possible to apply the ancient theory of meridians to the study of electric potential at well and sea points in branches of the twelves meridians.

• 약학회지
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• 제49권4호
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• pp.255-259
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• 2005

Financial standing of National Health Insurance has been experiencing a grave deterioration during the last 4-5 years, and the yearly amount paid by the insurance for drug expense rose up to 4 trillion won recently. Furthermore, the ratio of drug expenses in the total expenditure of the insurance reached about $25\%$, showing the tendency to be levelled off. As a measure to improve the financial deterioration of the insurance and to encourage generic substitution among the health professionals, we compared pharmacokinetic parameters of brand name drug (Lamisil) and generic drug (Muzonal) containing terbinafine HCl in healthy volunteers. The area under the curve (AUC) of the two drugs showed $2220.4\pm784.7\;and\;2143.1\pm861.6hr{\cdot}ng/ml$ in the corresponding order and no statistically significant difference was identified. The peak concentration $(C_{max})$ of the generic drug demonstrated $566.6\pm246.2 ng/ml$ compared to $550.8\pm204.0$ of brand name drug, which was not significantly different either. Time to reach peak concentration showed about 6 minutes difference between the drugs, which has no clinical significance to the treatment of dermatomycosis and dermatophytosis.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.114-133
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• 2003

Objective : The meridian theory in oriental medicine explains that Sp9(Yinlingquan) has been considered very important for gynecological disorders, spleen and stomach disorders, and water metabolic disorders. Functional MRI is the best method of showing the evidences of the effect of the Electro-acupuncture treatment through scientific methods. On this supposition, Electro-acupuncture stimulation on Sp9(Yinlingquan) was carried out on six healthy volunteers, using the gradient echo sequence with the 3.0T whole-body MRI system(ISOL). Methods : Electro-acupuncture stimulation on Sp9(Yinlingquan), the experiment was carried out on six healthy volunteers, using the gradient echo sequence with the 3.0T whole-body MRI system(ISOL). After the needle insertion on right Sp9(Yinlingquan), 2Hz of electric stimulation was given for 30 seconds, repeated five times, with 30 seconds' intervals. The Image analysis including motion correction, talairach transformation, and smoothing was done using SPM99. Results : The electro-acupuncture stimulation on Sp9(Yinlingquan) activates Brodmann Area 13, 19, 22, 39, 40, 47 which may be the central pathways of the electro-acupuncture stimulation on Sp9(Yinlingquan). We also hypothesize that those brain areas may be directly or indirectly related with the mechanism of the effect of electro-acupuncture stimulation on Sp9(Yinlingquan).