• 제목/요약/키워드: Blood plasma

검색결과 2,258건 처리시간 0.025초

성인병의 예방과 치료를 위한 영양과 운동처방 II. 고혈압과 동맥경화에 미치는 영향 (Exercise Prescription and Dietary Modification for Prevention and Treatment of Chronic Degenerative Disease II. On Arteriosclerosis and Hypertension)

  • 백영호
    • 생명과학회지
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    • 제9권2호
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    • pp.231-240
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    • 1999
  • 규칙적인 운동은 혈압을 낮춰주고 체중조절과 스트레스 해소에도 도움을 주기 때문에 협심증이나 심근경색과 같은 관상동맥질환을 예방하는데 효과가 있다. 동맥경화증을 촉진시키는 위험인자로는 고혈압, 고지혈증, 당뇨병, 비만, 지나친 흡연, 운동부족 등을 들 수 있으며, 동맥경화의 진행은 어려서부터 시작되어 연령의 증가와 어불어심해진다. 특히, 여자보다 남자에게서 더 심하다. 동맥경화증 위험인자가 있는 사람의 경우 식습관과 생활양식, 그리고 운동처방으로 동맥경화성 질환을 예방하는 것이 중요하다. 식이섬유는 체내에서 소화관의 운동을 촉진하여 장관내 체류기간을 단축시키며 콜레스테롤의 흡수를 저해하여 비만, 고지혈증, 동맥경화 및 대장암 등을 예방할 수 있다. 각종 채소류와 해조류는 불포화지방산이 다량으로 함유된 식품으로서 장내에서 콜레스테롤 흡수를 방해하는 역할을 한다. 또한 식물성 기름에 함유되어 있는 필수지방산과 불포화지방은 콜레스테롤의 대사를 촉진하는 반면 흡수를 방해하며, 과일류에는 수용성 식물섬유인 팩틴이 함유되어 있어 체내의 콜레스테롤치를 떨어뜨린다. 콜레스테롤 및 포화지방산이 적고 불포화지방산이 많은 음식을 섭취하도록 하며 식이요법만으로도 콜레스테롤치를 10~15% 감소시킬 수 있다. 운동과 식이를 병행하여 운동을 지속적으로 장기간 할 때 효과가 매우 크다. 운동은 유산소성 운동으로서 운동강도는 HRmax의 60~80$\%$ $Vo_2$ max 50~70$\%$), 운동시간은 15~60분/day, 운동빈도는 3-6회/week가 바람직하다. 특히 심한 고혈압의 경우에는 환자의 상태에 따른 운동처방의 배려가 있어야 되며, 의사와 상의하여 전문적인 처방이 필요하다. 확인되었다.H, ENO1, ADH1 promoter 순으로 나타났지만, 초기 포도당 농도가 높을 때나 에탄을 생산이 심각한 유가식 배양에서는 ENO1 promoter가 inulinase의 구성적 발현ㆍ생산에 더 적합할 것으로 사료된다.라서 체중조절을 위해서는 식이제한 보다는 자유로운 식이 섭취의 방법을 통해 더 많은 운동기간을 가지고 운동을 한다면 체중조절은 물론 근육 대사를 원활히 하여 건강한 생활을 할 수 있으리라 기대한다.공정에서 매우 효과적으로 이용될 수 있을 것으로 판단된다.게 기여하리라고 전망된다.

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Estimating total lysine requirement for optimised egg production of broiler breeder hens during the early-laying period

  • Kim, Eunjoo;Wickramasuriya, Samiru Sudharaka;Shin, Taeg Kyun;Cho, Hyun Min;Kim, Hyeun Bum;Heo, Jung Min
    • Journal of Animal Science and Technology
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    • 제62권4호
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    • pp.521-532
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    • 2020
  • The production performance of broiler breeder hens in response to different levels of total lysine during the early laying period was investigated. A total of 126 Ross 308 parent stock hens were offered one of seven dietary treatments formulating elevated contents of total lysine ranging from 0.55% to 0.79% (0.04 scale; 133 g of feed) from 23 to 29 weeks of age. Each treatment had six replicates with three birds per pen. Body weight was recorded triweekly and eggs were collected and weighted at 9:00 am daily. One hen from each pen was euthanized to collect blood samples and visceral organs were harvested and weighed. Egg production, egg weight and egg mass were lower (p < 0.05) in hens offered a diet containing 0.55% total lysine compared to those fed the diet containing higher total lysine. Hens offered a diet containing 0.71%, 0.75%, and 0.79% total lysine had greater (p = 0.008) egg production rate compared to those offered a diet containing lysine less than 0.71%. The number of total eggs produced tended to be greater (p = 0.083) in hens offered a diet containing 0.71 and 0.75% total lysine compared to the other treatments. The number of settable egg production was higher (p < 0.001) in hens offered a diet contacting 0.79% total lysine compared to those fed the diet containing lower levels of total lysine. The relative weights of oviduct and ovary were lower (p < 0.05) in hens offered a diet containing 0.59% total lysine compared to the other treatments. No difference found in body weight, the number of total eggs, double-yolk eggs and abnormal shell eggs among the treatments. The urea nitrogen, estradiol-17 beta and progesterone in plasma were not affected by treatments. Based on linear- and quadratic-plateau models, total lysine requirements for egg production, settable egg production and egg mass at the early laying period were to be 0.73%, 0.77%, and 0.71%, respectively. Modern broiler breeder hens likely require higher total lysine than NRC recommendation in a diet for enhancing productivity during the early-laying period.

고지방과 콜레스테롤 식이로 유도된 고지혈증 흰쥐에서 노루궁뎅이버섯의 항고지혈증 효과 (The Antihyperlipidemic Effect of Lion's Mane Mushroom (Hericium erinaceus) in Hyperlipidemic Rats Induced by High Fat and Cholesterol Diet)

  • 장형석;윤기남
    • 대한임상검사과학회지
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    • 제49권3호
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    • pp.263-270
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    • 2017
  • 노루궁뎅이버섯의 자실체가 고지방과 콜레스테롤을 급여한 Sprague Dawley계 암컷 흰쥐의 지질대사와 생리활성에 미치는 영향을 조사하고자 생후 5주령의 흰쥐에 표준 식이를 급여한 정상군(NC군), 표준 식이에 15%의 돈지와 1%의 콜레스테롤을 첨가한 식이를 급여한 고지방 콜레스테롤군(HFC군), 고지방 콜레스테롤 식이에 노루궁뎅이버섯 자실체 분말을 5% 첨가한 군(HFC+HE군) 등 총 3개의 군으로 나누어 6주간 실험을 진행하였다. 실험동물의 체중증가와 식이효율은 HFC군에 비해 HFC+HE군이 유의하게 감소하여 NC군과 유사한 수준을 나타냈다. 식이섭취량은 NC군과 HFC군에 비해 HFC+HE군이 유의하게 낮았다. HFC+HE군의 혈청 총콜레스테롤, LDL-콜레스테롤의 농도는 NC군과 HFC군에 비해 유의하게 낮았고 동맥경화지수(AI)도 NC군과 HFC군에 비해 유의성 있게 낮았다. 그러나 혈청의 중성지방 농도는 NC군에 비해 유의성은 없었으나 HFC군에 비해 유의하게 낮았다. HFC+HE의 혈청 알부민, 크레아티닌, 요산 및 총단백질의 농도는 NC군의 수준을 나타냈다. 혈청의 AST, ALT 및 ALP 활성은 NC군과 유사하였으나 HFC군에 비해 유의하게 낮았다. 실험 5~6주에 배출된 변을 채취하여 총지질과 총콜레스테롤의 양을 분석한 결과 NC군과 HFC군에 비해 변의 총지질과 총콜레스테롤 함량이 유의하게 높아 변으로 배출된 총지질과 총콜레스테롤의 양이 많게 증가한 것으로 나타났다. 따라서 고지방 콜레스테롤식이에 5%의 노루궁뎅이버섯 자실체 분말을 첨가한 식이를 급여한 흰쥐의 체중은 정상군의 수준을 유지하였고, 혈청의 총콜레스테롤, LDL-콜레스테롤 및 중성지질의 농도도 정상군과 유사하게 낮았으며, 동맥경화지수도 낮아 노루궁뎅이버섯이 흰쥐의 지질대사를 정상으로 유지시키는 효과를 나타내는 것으로 사료되었다.

농촌 지역 주민의 혈청 Ferritin 수준과 대사증후군과의 관련성 (Serum Ferritin and Risk of the Metabolic Syndrome in Some Korean Rural Residents)

  • 류소연;김기순;박종;강명근;한미아
    • Journal of Preventive Medicine and Public Health
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    • 제41권2호
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    • pp.115-120
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    • 2008
  • Objectives : The purpose of this study was to examine the relationship between serum ferritin and the metabolic syndrome (MS). Methods : We conducted a cross-sectional study of 1,444 adults over age 40 and under age 70 that lived in a rural area and participated in a survey conducted as part of the Korean Rural Genomic Cohort Study (KRGCS). The MS was defined as the presence of at least three of the followings : elevated blood pressure, low high density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, or abdominal obesity. After adjustment for age, alcohol intake, menopausal status, body mass index (BMI), high sensitivity C-reactive protein (hs-CRP), and alanine aminotransferase (ALT), odds ratios (ORs) for the prevalence of the MS by sex were calculated for quartiles of serum ferritin using logistic regression analysis. Results : The MS was more common in those persons , with the highest levels of serum ferritin, compared to persons with the lowest levels, in men (37.1% vs. 22.4%, p=0.006) and women (58.8% vs. 34.8, p<0.001). In both sexes, the greater the number of MS components presents, the greater the serum ferritin levels. After adjustment for age, alcohol intake, and menopausal status, the OR for metabolic syndrome, comparing the fourth quartile of ferritin with the first quartile, was 2.21 (95% confidence interval; CI=1.26-3.87; p-trend=0.024) in men and 2.10 (95% CI=1.40-3.17; p-trend=0.001) in women. However, after further adjustment for BMI, hs-CRP, and ALT, the ORs were statistically attenuated in both sexes. Conclusions : Moderately elevated serum ferritin levels were not independently associated with the prevalence of the MS after adjusting for other risk factors. Further studies are needed to obtain evidence concerning the association between serum ferritin levels and the MS.

H2O2/HCl 처리한 Ti 임플란트의 생체활성 평가 (Evaluation of Bioactivity of Titanium Implant Treated with H2O2/HCl Solution)

  • 유재선;권오성;이오연;이민호;송기홍
    • 한국재료학회지
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    • 제15권5호
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    • pp.353-360
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    • 2005
  • Surface treatment play an important role in nucleating calcium phosphate deposition on surgical Ti implant. Therefore, the purpose of this study is to examine whether the precipitation of apatite on cp-Ti and Ti alloys are affected by surface modification in HCl and $H_2O_2$ solution. Specimens were then chemically treated with a solution containing 0.1 M HCl and 8.8M $H_2O_2$ at $80^{\circ}C$ for 30 mins, and subsequently heat-treated at $400^{\circ}C$ for 1 hour. All specimens were immersed in the HBSS with pH 7.4 at $36.5^{\circ}C$ for 15 days, and the surface was examined with XRD, SEM, EDX ana XPS. Also, pure Ti, Ti-6Al-4V and Ti-6Al-7Nb alloy specimens with and without surface treatment were implanted in the abdominal connective tissue of mice for 4 weeks. All specimens chemically treated with HCl and $H_2O_2$ solution have the ability to form a apatite layer in the HBSS which has inorganic ion composition similar to human blood plasma. The average thickness of the fibrous capsule surrounding the specimens implanted in the connective tissue was $38.57\;{\mu}m,\;62.27\;{\mu}m\;and\;45.64\;{\mu}m$ in the cp-Ti, Ti-6Al-4V ana Ti-6Al-7Nb alloy specimens with the chemical treatment respectively, and $52.20\;{\mu}m,\;75.62\;{\mu}m\;and\;66.56\;{\mu}m$ in the commercial specimens of cp-Ti, Ti-6Al-4V and Ti-6Al-7Nb without any treatment respectively. The results of this evaluation indicate that the chemically treated cp-Ti, Ti-6Al-4V ana Ti-6Al-7Nb alloys have better bioactivity and biocompatibility compared to the other metals tested.

항균성 Ag-30CaO·70SiO2 Gel의 MC3T3 세포적합성에 관한 연구 (Evaluate the Suitability of MC3T3 Cells to Antibacterial Ag-30CaO·70SiO2 Gel)

  • 윤금재;류재경;안응모;김윤종;김택남;노인섭;조성백
    • 한국재료학회지
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    • 제24권12호
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    • pp.671-676
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    • 2014
  • It is known that bones get damaged by accidents and aging. Since the discovery of Bioglass, various kinds of ceramics have been also found to bond to living bone; some of these ceramics are already being clinically used as bone-repairing materials. In the present study, antibacterial calcium silicate gel ($Ag-30CaO{\cdot}70SiO_2$ gel) was prepared by sol-gel method in order to control the microstructure, which is related to the dissolution rate and induction period of apatite formation in body environment. In addition, biological $Ag-30CaO{\cdot}70SiO_2$ is tested. This was done to impart antimicrobial activity to the $30CaO{\cdot}70SiO_2$. Ag ion was added during sol-gel synthesis to replace the $H_2O$ added during the making of the $30CaO{\cdot}70SiO_2$ gel, which has silver solutions of various concentration. After the sol-gel process, 1N-$HNO_3$ solution was used to wash the gel when synthesizing the gel, in order to maintain the porous structure and remove PEG, water soluble polymers. Then, the apatite forming ability of the sol-gel derived CaO-$SiO_2$ gels was investigated using simulated body fluid (SBF), which had almost the same ion concentration as that of human blood plasma. The gels were analyzed by FT-IR spectroscopy, SEM observation, XRD, and fluorescent microscopy. The apatite was successfully created even after washing the gel; apatite is present in an amorphous state, and was found to affect the concentration of the Ag ion in cells in MC3T3 live & dead assay results. From these results, it is suggested that a good material that can be used to repair defects of nature bone is $Ag-30CaO{\cdot}70SiO_2$ gel.

사육수의 저염분 변화에 따른 넙치(Paralichthys olivaceus)의 스트레스 반응 (Stress Responses of Olive Flounder Paralichthys olivaceus to Hyposalinity)

  • 이복규;박철환;김병기;허준욱;장영진;이종관;임영수;이종하
    • 한국양식학회지
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    • 제15권1호
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    • pp.69-75
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    • 2002
  • 사육수의 저염분에 따른 급성 스트레스 반응 (코티졸, 글루코스, Na$^{+}$, K$^{+}$, Cl ̄, 총단백질, ALT, AST, 헤마토크리트, 적혈구수, 헤모글로빈 농도, MCV, MCH 및 MCHC) 조사하였다. 예비사육 수조에서 사육하던 어류를 해수(35$\textperthousand$)가 공급되는 실험수조에서 30분이내에 담수 (0 $\textperthousand$)를 흘려주면서 l5 $\textperthousand$구와 0 $\textperthousand$구로 사육수를 교환하였다. 실험개시시 코티졸 농도는 1.6${\pm}$0.2 ng/$m\ell$로부터 15 $\textperthousand$구는 1시간째 3.5${\pm}$1.8 ng/$m\ell$, 3시간째와 24시간째에는 각각 1.7${\pm}$0.2 ng/$m\ell$와 3.0${\pm}$2.4 ng/$m\ell$로 유의한 차이를 보이지 않았다. 그러나 0 $\textperthousand$구는 1시간째 22.8${\pm}$3.8 ng/$m\ell$, 3시간째 9.3${\pm}$1.8 ng/$m\ell$, 24시간째 9.5${\pm}$0.2 ng/$m\ell$로 높아진 값을 보였다. 글루코스 함량은 실험개시시 17.7${\pm}$0.6 mg/dl로부터 15$\textperthousand$구와 0$\textperthousand$구는 1시간째 각각 96.2${\pm}$1.6 mg/dl, 155.8${\pm}$16.0 mg/dl로 높아졌다. 그러나 24시간째에는 각각 13.0${\pm}$3.2 mg/dl, 15.2${\pm}$1.4 mg/dl로 실험개시시 값으로 회복되었다. Na$^{+}$과 K$^{+}$은 15 $\textperthousand$구에서 차이를 보이지 않았으나, 0 $\textperthousand$구에서는 감소하는 경향을 보였다. 생존율은 48시간째부터 폐사하기 시작하여 144시간째에는 전량폐사하였다. 삼투압 조절 능력을 위한 여러가지 파라메타에서 15 $\textperthousand$구는 이상이 없는 것으로 추측되나, 0 $\textperthousand$구에서는 코티졸, Na$^{+}$, K$^{+}$, Cl ̄, 총단백질 및 AST에서 시간경과에 따른 삼투압 조절 능력에 문제가 있는 것으로 보여진다.

Zinc 투여가 Streptozotocin 유발 당뇨쥐의 항산화효소계와 Metallothionein합성에 미치는 영향 (Effects of Zinc on the Antioxidative Enzymatic System and Metallothionein Synthesis in Streptozotocin-induced Diabetic Rats)

  • 최원경;이순재
    • 한국식품영양과학회지
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    • 제26권2호
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    • pp.344-350
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    • 1997
  • 당뇨병쥐에 있어서 생체내 항산화방어계에 미치는 zinc투여의 영향을 관찰하기 위하여 비타민 E 투여군과 비교실험하였다. 혈당량은 당뇨군들이 대조군에 비해 현저히 증가되었으나 ZDM군이 DM과 EDM군에 비해 약간 감소되는 경향을 띠었다. 혈장 인슐린수준은 혈당량과 반대의 경향을 띠었다. 간조직중의 TBARS 축적량은 대조군에 비해 DM군은 2.3배 높았고 ZDM군은 DM에 비해 낮아졌으며, EDM군은 대조군과 비슷하였다. 간조직중의 환원형 glutathione(GSH) 함량은 대조군에 비해 DM군은 감소되었으나 ZDM과 EDM군은 DM군에 비해 각각 2.3, 1.7배씩 증가되었다. 산화형 GSH함량은 대조군에 비해 DM군이 증가되었고, DM군에 비해 ZDM군과 EDM군 모두 감소하였으며 GSH/GSSG비는 GSH비와 비슷한 경향이었다. 간조직중의 SOD, GSH-Px, GST활성은 모두 대조군에 비해 DM군은 유의적으로 감소되었으나 ZDM, EDM군은 DM군에 비해 증가되었다. 간장과 신장에서의 metallotruonein 함량은 모두 대조군에 비해 DM, EDM군은 증가하였고, ZDM군은 20배, 5.3배 각각 현저히 증가하였다.

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조프란 정(온단세트론 8mg)에 대한 온프란 정의 생물학적동등성 (Bioequivalence of Onfran Tablet to Zofran Tablet (Ondansetron 8mg))

  • 신인철;홍정욱;박윤영;고현철
    • Biomolecules & Therapeutics
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    • 제11권1호
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    • pp.58-64
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    • 2003
  • Ondansetron is a potent, highly selective 5-hydroxytryptamin $e_3$(5-H $T_3$) receptor-antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, Zofran (Glaxo Smithcline Korea Ltd.) and Onfran (Korea United Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 24.39$\pm$1.69 year in age and 69.00$\pm$6.74kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 8mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AVC, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC, $C_{max}$ and T max between two tablets were 5.83%, 5.75% and -5.71%, respectively when calculated against the Zofran, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were above 90%, above 90% and below 60%, respectively. Minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 were less than 20% (e.g., 12.74% and 11.78% for AUC and $C_{max}$ respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20% (e.g., 34.22%). The 90% confidence intervals were within $\pm$20% (e.g., -2.73∼14.39 and -2.16∼13.67 for AUC and $C_{max}$ respectively). But 90% confidence intervals for $T_{max}$ were not within $\pm$20% (e.g., -28.71∼17.28). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant difference in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20% (e.g., 5.83% and 5.75% for AUC and $C_{max}$ respectively). The 90% confidence intervals for the log transformed data were the acceptance range of log 0.8 to log 1.25 (e.g., log 0.99∼log 1.15 and log 0.98∼log 1.15 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$, met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofrm1 tablet.t is bioequivalent to Zofrm1 tablet.m1 tablet.m1 tablet.m1 tablet.

라미실 정(테르비나핀 125mg)에 대한 터비넥스 정의 생물학적동등성 (Bioequivalence of Terbinex Tablet to Lamisil Tablet (Terbinafine 125mg))

  • 고현철;홍정희;신인철
    • Biomolecules & Therapeutics
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    • 제11권1호
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    • pp.65-71
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    • 2003
  • Terbinafine is a synthetic allylamine that is available in an oral formulation and is used at a dosage of 250mg/day. It is used as an active antifungal agent and inhibits the fungal enzyme squalene epoxidase, which leads to the accumulation of the sterol squalene, which is toxic to the organism. The purpose of the present study was to evaluate the bioequivalence of two terbinafine tablets, Lamisil (Novartis Korea Ltd.) and Terbinex (C-TRI Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 26.00$\pm$2.57 year in age and 70.51$\pm$9.36 kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 125 mg of terbinafine was orally administered, blood was taken at predetermined time intervals and the concentrations of terbinafine in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AUC, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC, $C_{max}$ and $T_{max}$ between two tablets were -4.191%, 5.223% and -25.720%, respectively when calculated against the Lamisil, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were 81%, 87% and below 60%, respectively. Minimum detectable differences(.il) at alpha=O.1 and 1-/3=0.8 were less than 20% (e.g., 19.72% and 17.77% for AUC and $C_{max}$, respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20% (e.g., 26.25%). The 90% confidence intervals were within $\pm$20% (e.g., -17.440∼9.06 and -6.713∼17.160 for AUC and $C_{max}$ respectively). But 90% confidence intervals for $T_{max}$ were not within $\pm$20% (e.g., -43.346∼8.083). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant differences in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20% (e.g., -4.19% and 5.22% for AUC and $C_{max}$, respectively). The 90% confidence intervals for the log transformed data were not the acceptance range of log 0.8 to log 1.25 in AUC but the acceptance range of log 0.8 to log 1.25 in $C_{max}$ (e.g., log 1.13∼log 1.50 and log 0.94-log 1.22 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA (1998 year) for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofran tablet. But in another ANOVA test AUC did not meet the criteria of KFDA (2002) for bioequivalence but $C_{max}$ met the criteria of KFDA (2002 year) for bioequivalence.or bioequivalence.equivalence.equivalence.equivalence.