• 한국응용과학기술학회지
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• 제36권1호
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• pp.34-46
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• 2019

비만은 대사증후군과 밀접한 관련이 있다. 본 연구는 8주간 고지방식이를 섭취한 쥐에서 고지혈증 치료제인 피노피브레이트(fenofibrate) 단독처방, 수영운동 단독처방 및 fenofibrate와 수영운동의 병합처방이 비만을 조절하는지를 조사하고, fenofibrate와 수영운동의 병합처방이 fenofibrate 단독처방에 비해 효과적으로 비만을 조절하는지를 분석하였다. Fenofibrate 단독처방과 수영운동 단독처방 모두 대조군에 비해 비만과 관련된 요소들인 몸무게, 지방무게, 혈청 지질성분 및 지방세포 크기를 감소시켰다. 쥐는 fenofibrate와 수영운동의 병합처방 되었을 경우 fenofibrate 단독처방 되었을 경우에 비해 비만과 관련된 요소들이 더 효과적으로 감소되었다. 대조군에 비해 fenofibrate 단독처방, 수영운동 단독처방 및 fenofibrate와 수영운동의 병합처방 모두 혈청 포도당 수치를 감소시켰다. 본 연구는 fenofibrate와 수영운동의 병합처방이 비만과 혈당을 효과적으로 조절함으로써 고지방식이 섭취로 인해 발생되는 대사증후군의 억제에 공헌할 것임을 제시하고 있다.

• 대한의생명과학회지
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• 제18권4호
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• pp.355-361
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• 2012

We investigated to verify whether the $PPAR{\alpha}$ agonist fenofibrate regulates adipose tissue metabolism and to determine the molecular mechanism involved in this regulation. After male mice (C57BL/6J) received a high fat diet with or without fenofibrate for 6 weeks, the effects of fenofibrate on not only adipose tissue weight, visceral adipocyte size, serum lipid and glucose levels, but also the expression of uncoupling proteins (UCPs). Mice given a fenofibrate-supplemented high fat diet showed reduced both visceral and subcutaneous adipose tissue weights versus high fat diet-fed animals. The size of visceral adipocytes was significantly decreased by fenofibrate treatment. The administration of fenofibrate resulted in decreased serum levels of triglycerides, free fatty acids, and glucose. Moreover, fenofibrate up-regulated mRNA levels of visceral adipose tissue UCP2 and skeletal muscle UCP3. Therefore, our results suggest that the increases in the expression of UCPs by fenofibrate seem to suppress diet-induced visceral adiposity as well as severe hypertriglyceridemia and hyperglycemia in male mice.

• 대한의생명과학회지
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• 제19권1호
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• pp.17-24
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• 2013

Animals show a sexual dimorphism in metabolic responses. We investigated to verify whether the peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) agonist fenofibrate regulates obesity and skeletal muscle lipid metabolism with sexual dimorphism and to determine the changes in skeletal muscle expression of $PPAR{\alpha}$ target genes. After both sexes of C57BL/6J mice received a high fat diet with or without fenofibrate for 7 weeks, we examined the effects of fenofibrate on not only body weight, adipose tissue mass, and skeletal muscle lipid accumulation, but also the mRNA expression of $PPAR{\alpha}$-related genes in skeletal muscle. Male mice given a fenofibrate-supplemented high fat diet showed decreased body weight gain and adipose tissue mass compared with mice fed a high fat diet alone, whereas fenofibrate did not reduce them in high fat diet-fed female mice. Lipid accumulation in skeletal muscle was inhibited by fenofibrate in male mice, but not in female mice. Gene expression analysis revealed that fenofibrate increased the mRNA levels of $PPAR{\alpha}$ target enzymes only in male mice. Therefore, our results suggest that sex-dependence differences in obesity and intramuscular lipid levels under fenofibrate treatment could be due in part to the differences in skeletal muscle $PPAR{\alpha}$ activation between male and female mice.

• 약학회지
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• 제59권3호
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• pp.98-106
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• 2015

Analytical method for related substances can be categorized into two methods depending on the necessity of reference standard (RS). The analytical method of related substances with RS is fast and accurate, but it's very expensive and technically difficult to synthesize RS due to their complicated structure. Another method is using relative retention time (RRT) and relative response factor (RRF) which are already validated with RS. Validation of this method is not easy and time consuming, but once it has been developed, it can save cost and time. In this study, we developed the analytical method for related substances of fenofibrate using RRT and RRF. We validated the method by evaluating specificity, linearity, accuracy and precision according to the "Manual for Guideline Application for Validation of Analytical Procedures" of MFDS. Also, we calculated RRT and RRF between fenofibrate and fenofibrate related substances. The results of this study showed high specificity for fenofibrate and fenofibrate related substances. Correlation coefficient(r) of all substances were more than 0.99, and the recovery of fenofibrate, fenofibrate related substance I, II and III were 99.44%, 100.84%, 99.14% and 101.58%, respectively. Precision of fenofibrate and its related substances were ranged between RSD 0.29% and 0.93%. Quantification limits of fenofibrate, fenofibrate related substance I, II and III were determined to be $0.03{\mu}g/ml$, $0.05{\mu}g/ml$, $0.04{\mu}g/ml$ and $0.02{\mu}g/ml$, respectively by confirming signal to noise ratio of each chromatogram. The RRT for fenofibrate related substance I, II and III were determined to be 0.35, 0.41 and 1.34, respectively. Also, the RRF for fenofibrate related substance I, II and III were determined to be 1.28, 0.98 and 0.79, respectively. The developed method was applied to determine contents for fenofibrate related substances in commercial fenofibrate (active pharmaceutical ingredient). As a result, developed analytical methods of related substances will be used for revising the monograph of fenofibrate in Korean Pharmacopoeia revision and contribute quality control of drugs by improving cost and time consuming problem of RS.

• 한국응용과학기술학회지
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• 제36권4호
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• pp.1172-1180
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• 2019

본 연구는 저지방식이를 섭취한 난소절제 암컷 쥐에서 피노피브레이트(fenofibrate) 단독처리 및 피노피브레이트와 17베타-에스트라다이올(17β-estradiol)과의 동시처리가 혈청 속 지질대사를 조절하는지를 조사하였고, 피노피브레이트와 17베타-에스트라다이올의 동시처리에 의해 혈청 속 지질대사에 대한 피노피브레이트 단독처리의 효과가 어떻게 조절되는지를 연구하였다. 저지방식이만을 섭취한 대조군에 비해 피노피브레이트가 단독처리된 쥐와 피노피브레이트와 17베타-에스트라다이올이 동시처리된 쥐의 8주째 몸무게는 감소되지 않았다. 피노피브레이트 단독처리와 피노피브레이트와 17베타-에스트라다이올 동시처리는 혈청 속 총 콜레스테롤과 HDL-콜레스테롤을 감소시키지 않았다. 피노피브레이트는 대조군에 비해 혈청 속 LDL-콜레스테롤과 중성지방을 감소시켰다. 피노피브레이트 단독처리에 비해 피노피브레이트와 17베타-에스트라다이올 동시처리는 혈청 속 중성지방에 대해 유익한 변화를 나타내었다. 따라서 본 연구는 저지방식이를 섭취한 난소절제 암컷 쥐에서 fenofibtae 단독처리에 의해 감소된 혈청 속 중성지방은 피노피브레이트와 17베타-에스트라다이올의 동시처리에 의해 개선될 수 있음을 발견하였다.

• BMB Reports
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• 제42권10호
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• pp.679-684
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• 2009

Fenofibrate has been proven to reduce adiposity. Since gestation produces an increase in white adipose tissue (WAT) mass, we comparatively studied this drug-effect in virgin and pregnant rats. Fenofibrate reduced lumbar WAT weight in both pregnant and virgin rats. Fenofibrate treatment did not modify plasma free fatty acid (FFA) concentration in virgin rats, it greatly increased it in pregnant animals. Remarkable differences between the two groups were obtained for two proteins related to fatty acid oxidation and esterification and storing. Respectively, the mRNA levels of carnitine palmitoyltransferase I (CPT-I) were increased by the fenofibrate only in the virgin rats and a similar finding was observed for the expression of phosphoenolpyruvate carboxykinase (PEPCK). These findings indicate that fenofibrate reduces adiposity in pregnant and virgin rats through different mechanisms: a) in virgin rats, by promoting fatty acid oxidation; and b) in pregnant rats, by enhancing fatty acid output.

• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.339-345
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• 2010

Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

• 한국응용과학기술학회지
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• 제40권1호
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• pp.1-12
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• 2023

고지방식이를 섭취한 수컷 쥐에서 PPARα activator fenofibrate 단독처방(H/F)과 수영운동 단독처방(H/S)에 비해 fenofibrate와 수영운동의 조합처방(H/F/S)이 백색지방조직의 염증 개선에 유익한 상승효과를 나타낼 것인지를 조사하였다. 몸무게, 체내 백색지방조직의 무게 및 혈청 총 콜레스테롤 수치는 저지방식이를 섭취한 쥐(L)에 비해 고지방식이를 섭취한 쥐(H)가 증가하였으며, H에 비해 H/F와 H/S 모두 감소하였으며, fenofibrate에 의해 감소된 수치는 fenofibrate와 수영운동의 조합처방(H/F/S)에 의해 더 효과적으로 감소하였다. 체내 백색지방조직에서 염증성 사이토카인 유전자와 지방산 산화 관련 유전자의 발현을 조사한 결과, L에 비해 H는 증가하였으며, H에 비해 H/F와 H/S 모두 감소하였고, H/F/S는 H/F에 비해 더욱 감소시켰다. 따라서 본 연구는 고지방식이를 섭취한 수컷 쥐에서 fenofibrate와 수영운동의 조합처방은 fenofibrate 단독처방에 비해 지방산 산화를 촉진하여 비만으로 발생한 백색지방조직의 염증을 더욱 효과적으로 억제한다는 것을 밝힘으로써, 비만으로 발생하는 지방조직의 염증을 개선하는 실질적인 방법을 제시하였다.

• 한국임상약학회지
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• 제22권3호
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• pp.195-201
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• 2012

목적: 이상지방혈증 환자의 치료는 우선적으로 저밀도지단백을 감소시키고, 저밀도지단백이 목표수치에 도달한 이후에도 혈중 중성지방이 높을 경우 nicotinic acid 또는 fibrate를 사용하도록 권장되고 있다. 본 연구는 이상지방혈증이 있는 환자에서 acipimox의 효과를 fenofibrate와 비교하여 분석하고자 시행되었다. 방법: 본 연구는 서울에 있는 한 3차 대학병원의 환자를 대상으로 후향적으로 의무기록을 분석하여 시행되었다. 혈중 중성지방 농도가 200 mg/dL 이상으로써 acipimox 또는 fenofibrate를 신규처방 받은 환자를 대상으로 각각의 약물이 지단백에 미치는 영향을 36주간 추적하여 비교분석 하였다. 결과: Acipimox를 투여 받은 환자 41명, fenofibrate를 투여 받은 환자 62명이 모집되었으며, 각각의 약물을 복용한 환자군의 기본적인 인구학적인 특성은 유의하게 상이하지 않았다. 3개월 간의 약물투여 후 두 약물군 환자 모두에서 총콜레스테롤(p < 0.05) 및 저밀도지단백(p < 0.001)이 약물투여 전과 비교하였을 때 유의하게 감소하였고, 고밀도지단백은 모든 환자에서 유의하게 증가하였다(p < 0.05). 한편 중성지방 감소율은 acipimox군이 fenofibrate군에서보다 더 크게 나타났다(p < 0.05). 약물유해반응의 빈도는 두 약물군 간에 유의한 차이가 없었다. 결론: 총콜레스테롤, 저밀도지단백 콜레스테롤 등을 감소시키거나 고밀도지단백 콜레스테롤을 증가시키는 효과는 acipimox와 fenofibrate가 유의하게 다르지 않았으며, 중성지방을 감소시키는 효과는 acipimox가 fenofibrate보다 우월하였다.

• 약학회지
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• 제45권5호
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• pp.468-475
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• 2001

Fenofibrate is a fibric acid derivative that is a strong reducer of triglyceride. Micronozed formulation of fenofibrate has improved bioavailability compared to non-micrornized formulation. This study performed a retrospective comparison of micrornized and non-micrornized fenofibrate (28 in micronized and 51 in non-micronized group) by comparing the means of changes in total triglyceride, total cholesterol, HDL-cholesterol and TC/HDL ratio in type 2 diabetics with dyslipidemia The result skewed that after 12 weeks of treatment both drugs produced a significant reduction in total triglyceride levels (62% with micronized, 37% with non-micronized). The mean decrease observed for total triglyceride levels were significantly lower for micronized fenofibrate (p<0.001). Both drugs showed a significant reduction for total cholesterol levels (-22% with micronized, -14% with non-micronized fenofibrate). The mean decrease observed for total cholesterol was not significantly different between the two drugs (p>0.05). HDL-cholesterol levels increased by 24% and 15%) with micronized and non-micronized, respectively and the differences from the baseline were statistically significant for both drugs (p<0.05). The mean change of HDL-cholesterol was not significantly different between the two drugs. There was a statistically significant reduction in TC/HBL-cholesterol ratio from baseline for both drugs (7.1 to 4.8 with micronized and 5.1 to 4.5 with non-micronized), and the reduction of TC/HDL-cholesterol ratio tended to be significantly greater with micronized fenofibrate (p<0.05). This study shows that short-term treatment with micronized fenofibrate is more effective than non-micronized fenosbrate in type 2 diabetes patients with dyslipidemia.