• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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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 Biomedical Engineering Research
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• v.36 no.4
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• pp.95-102
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• 2015

Epilepsy is a chronic neurological disease which produces repeated seizures. Over 30% of epileptic patients cannot be treated with anti-epileptic drugs, and surgical resection may cause loss of brain functions. Seizure suppression by electrical stimulation is currently being investigated as a new treatment method as clinical evidence has shown that electrical stimulation to brain could suppress seizure activity. In this paper, design of a real-time closed-loop neurostimulation system for epileptic seizure suppression is presented. The system records neural signals, detects seizures and delivers electrical stimulation. The system consists of a 6-channel electrode, front-end amplifiers, a data acquisition board by National Instruments, and a neurostimulator and Generic Osorio-Frei algorithm was applied for seizure detection. The algorithm was verified through simulation using electroencephalogram data, and the operation of whole system was verified through simulation and in- vivo test.

• The Korean Journal of Applied Statistics
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• v.18 no.1
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• pp.159-171
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• 2005

The US Food and Drug Administration(FDA) recommends that population bioequivalence and individual bioequivalence would be assessed to address the prescribability and switchability between a brand-name drug and its new formulation or generic copy in its 2001 guidance document. The test for population bioequivalence in the latest FDA guidance is recommended in 2 x 4 crossover design, but it turns out to be very conservative. Recently Lee, Shao & Chow(2002), Chow, Shao & Wang(2003) and McNally, Iyer & Mathew(2002) proposed new statistical methods for assessing population bioequivalence between drugs to correct the biasness of current FDA method. Since 2 x 2 crossover experiment is most welcomed design in bioequivalence testing, we adopt their methods to 2 x 2 crossover designs and compare their methodologies with FDA one through the simulation study.

• Toxicological Research
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• v.21 no.3
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• pp.209-218
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• 2005

We investigated effects of recombinant human erythropoietin (rHuEPO) on profiles of mRNA transcripts in 6 male cynomolgus (M. fascicularis) monkey's spleen for 4 weeks. Six monkeys, composed of control and treatment group (Control : M1, M2, M3: Treatment : M4, M5, M6) were intravenously administered 3 times per week without or with a dose of rHuEPO 2730 IU/0.1 ml/kg. After 4 weeks rHuEPO treatment, spleen was removed for RNA isolation. Splenic gene expression was assessed using Affymetrix U133A 2.0 arrays containing 18,400 transcripts and variants, including 14,500 well-characterized human genes. Gene expression pattern was very different between individuals even in same treatment. In rHuEPO treated groups showed number of genes were up- or down-regulated (M4: 79: M5: 48; M6: 73 genes). Six genes (epidermal growth factor receptor, calgranulin A, estrogen receptor binding site associated antigen, matrix metalloproteinase 19, zinc finger and BTB domain containing 16, progestin and adipoQ receptor) were commonly expressed in rHuEPO treated group. The different individual response could be major considering factor in monkey experiment. Further study is needed to clarify the different individual response to rHuEPO in molecular level. This study will be valuable in the fundamental understanding and validation of molecular toxicology for bio-generic drugs including rHuEPO in cynomolgus monkey.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.574-579
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• 2008

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

• Journal of Food Hygiene and Safety
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• v.20 no.2
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• pp.77-82
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• 2005

Niacin (vitamin $B_{3}$) is the generic term for nicotinic acid (pyridine 3-carboxylic acid) and nicotinamide (nicotinic acid amide), and coenzyme forms of the vitamin. Large doses of nicotinic acid are associated with a number of adverse effects in human. The effects include flushing, skin itching, nausea, vomiting and gastrointestinal disturbance. This study was conducted to estimate daily intake of niacin by ingestion of food and multivitamin, and to identify risk value related with side effects, which can be caused by large dose intake in population having a typical lifestyle. Induced risk values by comparing only dietary intake level and intake level from both food and multivitamin with upper level as 35 mg/day were 0.53 and $0.81\~6.24$ respectively. Hazard Index over 1 means that occurrence of side effects would be expected in some population. When people intake multivitamin and functional food including niacin, risk value may increase more than risk value identified in this study.

• Journal of the Korean Data and Information Science Society
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• v.28 no.4
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• pp.743-754
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• 2017

Assessing bioequivalence between original drug and generic drug is traditionally based on $2{\times}2$ crossover design. As bioequivalence trials for highly variable drugs are getting popular, the required sample size based on $2{\times}2$ crossover design would be very large, which might cause the ethical concerns. Regulatory agencies like EMA and MFDS recommended higher order crossover designs such as $2{\times}4$, $4{\times}2$ and $4{\times}4$ crossover designs. Alternatively, a $2{\times}3$ dual design may be recommended in terms of economical and ethical points of view in comparison with the $2{\times}4$ crossover design for highly variable drug. In this study, we consider some statistical characteristics of $2{\times}3$ dual design and propose statistical procedures for calculating sample size and assessing bioequivalence based on $2{\times}3$ dual design. We also discuss the proposed procedures from the perspective of newly revised bioequivalence guidance issued by MFDS.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.219-226
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• 1990

Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical ($Vasotec^{\circledR}$, 61.38 ng/ml; $Beartec^{\circledR}$, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for $Vasotec^{\circledR}$ and $Beartec^{\circledR}$ tablets are presented in that order; area under the curve=330.63:320.96 $ng{\cdot}hr/ml$; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.14 no.1
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• pp.19-42
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• 2008

Blood-Letting Therapy is a rational and ecological medical treatment by which we can heal most of the diseases by removing the static blood which precipitates in the blood vessel and blocks the flowing of blood. And the static blood is the generic term for the injurious, bad, dead and precipitated blood which is blocked the capillary vessel. The Yellow Emperor's Canon of Internal Medicine says that "the patient is treated with drugs internally and stone acupuncture externally. "In the old texts, the blood-letting therapy is mentioned as blood-letting, network vessel pricking, bloodletting, pricking, and arousing pulses etc and it is noted down as the method of network vessel pricking in 'On the Application of Needles' of Spiritual Pivot. Nine-pricking therapy, twelve-pricking therapy and five-pricking therapy are recorded in the methods of network vessel pricking and among them, the method of squeezing blood after pricking the affected part is explained as the network vessel pricking. There are four methods of network vessel pricking, pricking, picking, cluster needling and scatter-pricking and they are fluidly applied to the various symptoms of diseases. In 'On Discriminative Treating for Patients of Different Regions' in Elementary Questions, Ki-baek emphasizes "most of the local people, there are black in skin and loose in striate, and their diseases are mostly of carbuncle kind. It is suitable to treat the disease with stone therapy to prick with stone, so the stone therapy is transmitted from the east. "And in 'On the Corresponding Relation Between the Eum and Yang of Man and All Things' in Elementary Questions, when the Emperor asked Ki-Back, he answered "sthenia means the sthenia of evil, and deficiency means the deficiency of healthy energy. When the blood is sthenic, the evil should be discharged by pricking when out letting the blood; deficiency of vital energy is the asthenia of channels and network vessels, so the energy should drain from the channel which is not deficient, to replenish. "And in this case we can use the methods of 'Breaking out the static bloods', 'driving out the static bloods', blood-letting'. With this we can infer that the blood-letting therapy is made use of the important medical treatments from the ancient times. Especially in referring to the principles of treatment in The Yellow Emperor's Canon of Internal Medicine, it mostly alluded to acupuncture therapies and only eleven times to medicinal treatments. This is to verify that the blood-letting therapy formed the foundation of the medical art. In Dong's Therapy of Acupuncture-Moxibustion and Bloodletting, Dong Kyeong-Chang gave emphasis on the points that there must be extravasated bloods without exception in the serious illnesses which is old, unnatural, accompanying acute pains and so we can revive our body‘s sprit by circulating 'gi' and static blood piled up in the network vessel, regulating the weakness and strength, and controling the disharmony of the internal organs. The blood-letting therapy has effect on the orifice in emergency, such as fore draining, freeing network vessels, harmonizing gi and blood, relieving pain, dispersing swelling and concretion, sedation, resolving toxin as well as strengthening the heart, relieving itching. So it has distinguished effect on all kinds of medical treatment to the modern people. But by the change of social customs and the confucianism of confucius - it is widely spread on the period of North and South Dynasties, 'Wi' and 'Jin' in china and the period of the Three States in korea - The blood-letting therapy which was regarded as the most important medicinal treatment withered rapidly. And Confucius accentuated the importance of our body and all its members, loyalty and filial piety and banned any damage of our body under no circumstances. As a result of it, the therapy of blood-letting had a rapid decrease and barely kept itself in existence in both countries. What is worse, at the period of Japanese colonial rule of korea and our nation's founding of early stage, it has been withered by the high-handed policy to change Oriental Medicine into modern medical science. So the therapy of blood-letting barely kept itself in existence in some Buddhist temples. Another case, it has handed down as a old-fashioned quick fix in folk remedies. But all kinds of the contamination of heavy metals and the misuses of antibiotics are widely spread nowadays, which increased diseases of adult people and incurable diseases as modern society unavoidably made its way into a highly industrial society. To make us more miserable, the western medical science - the antibiotics and surgical operation medical science - already reveals itself into a limit. The necessity of a new medical science which can give a security to the patients who are suffering from the diseases of adult people and the incurable diseases is especially come into the force nowadays. In view of the results after bibliographically studying on the blood-letting Therapy in Elementary Questions of the Yellow Emperor's Canon of Internal Medicine, the blood-letting therapy has acted for the important Oriental medicinal science and has been clarified the prominent effects on the diseases of adult people and the incurable diseases. So it is regarded as an appropriate thing that we lay out a determined theory of the blood-letting therapy and of course prevent the unwanted side effects from inappropriate medicinal treatments, and make full use of clinic by elevating the curative value and that we win back our self-respect of medical treatment which is dominated from the western medical science and ultimately contribute to national medical welfare.