• Journal of Pharmaceutical Investigation
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• 제33권3호
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• pp.171-178
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterzed by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. The purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$, and AUC. Administration of metformin in normal and diabetic rats treated with Laminaria japonica diet showed significant decrease in AUC, $C_{max},\;and\;k_a$, and increase in $t_{max}$, compared to those with normal diet. This might result from adsortion of metformin on components of Laminaria japonica, causing delayed absorption. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by long-term Laminaria japonica diet.

• 대한임상검사과학회지
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• 제52권3호
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• pp.253-260
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• 2020

알츠하이머 병은 인지 기능 저하로 인한 치매 발생으로 설명할 수 있는 만성 및 진행성 신경 퇴행성 질환이다. 알츠하이머 병의 특징은 세포 외 및 세포 내 아밀로이드 플라크의 형성이다. 아밀로이드 베타는 알츠하이머 병의 특징이며 미세아교세포는 아밀로이드 베타의 존재하에 활성화될 수 있다. 활성화된 미세아교세포는 전 염증성 사이토카인을 분비한다. 게다가, S100A9는 염증의 중요한 선천성 전 염증 기여자이며 알츠하이머 병에 잠재적인 기여자로 알려져 있다. 이 연구는 아밀로이드 베타 및 S100A9이 처리된 BV-2 세포에서 염증반응 및 NLRP3 인플라마솜 활성화에 대한 메트포르민 및 알파리포산의 효과를 조사했다. 메트포르민과 알파-리포산은 종양 괴사 인자-알파 및 일터루킨-6와 같은 염증성 사이토카인을 약화시킨다. 또한 메트포르민과 알파-리포산은 JNK, ERK, p38의 인산화를 억제하고, NF-kB 경로 및 NLRP3 인플라마솜의 활성화를 억제했다. 또한 메트포르민과 알파-리포산은 M1 표현형인 ICAM1의 수준을 감소시킨 반면 M2 표현형인 ARG1은 증가시켰다. 이러한 발견은 메트포르민과 알파-리포산이 아밀로이드베타 및 S100A9에 의한 신경 염증 반응에 대한 치료제가 될 수 있음을 시사한다.

• 대한임상독성학회지
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• 제16권2호
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• pp.165-171
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• 2018

An overdose of antihypertensive agents, such calcium channel blockers (CCBs) and angiotensin II receptor blocker (ARBs), and the antihyperglycemic agent, metformin, leads to hypotension and lactic acidosis, respectively. A 40-year-old hypertensive and diabetic man with hyperlipidemia and a weight of 110 kg presented to the emergency room with vomiting, dizziness, and hypotension following an attempted drug overdose suicide with combined CCBs, ARBs, 3-hydroxy-3-methylglutaryl-coemzyme A reductase inhibitors, and metformins. A conventional medical treatment initially administered proved ineffective. The treatment was then changed to simultaneous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), which was effective. This shows that simultaneous ECMO and CRRT can be an effective treatment protocol in cases of ineffective conventional medical therapy for hypotension and lactic acidosis due to an overdose of antihypertensive agents and metformin, respectively.

• 대한약침학회지
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• 제17권1호
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• pp.13-19
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• 2014

Objectives: The present study investigated the protective effect of Wattakaka (W.) volubilis leaf extract against streptozotocin (STZ)-induced diabetes in rats. Methods: Male Wistar rats were divided into five groups (with six rats in each group) and were fed ad libitum. The rats were fasted for sixteen hours before diabetes was induced by injecting a single dose of 90 mg/kg body weight of STZ in 0.9-percent normal saline through an intraperitoneal route. The five groups were as follows: Group 1: normal control (saline-treated), Group 2: untreated diabetic rats, Groups 3 and 4: diabetic rats treated orally with petroleum ether cold maceration extract (PEME) of W. volubilis (50 and 100 mg/kg body weight), and Group 5: diabetic rats treated orally with metformin (250 mg/kg body weight). All rats received treatment for 21 days. For the STZ-induced diabetic rats, the blood-glucose, ${\alpha}$-amylase, total protein and alanine transaminase (ALT) levels were measured on days 7, 14 and 21 of the treatment with PEME of W. volubilis and the treatment with metformin. Histopathological changes in the liver were examined with hematoxylin-eosin staining. Morphological changes in the liver were also examined with glutaraldehyde fixation. Results: The treatments with PEME of W. volubilis and with metformin in experimental rats by oral injections for 21 days produced reductions in the levels of serum biochemical markers. Histopathology and scanning electron microscopy results showed that the administrations of PEME of W. volubilis and of metformin suppressed the generation of abnormal liver cells in the STZ-treated rats. Conclusion: These results suggest that both PEME of W. volubilis and metformin have a protective effect against STZ-induced diabetes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2351-2354
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• 2015

In this study, the antiproliferative effects of the metformin was evaluated on MCF-7 Cells (human breast adenocarcinoma cell line). For this purpose cell kinetic parameters including cell proliferation assay, mitotic index and labelling index analysis were used. $30{\mu}M$, $65{\mu}M$ and $130{\mu}M$ Metformin doses were applied to cells for 24, 48 and 72 hours. The results showed that there was a significant decrease in cell proliferation, mitotic index and labelling index for all experimental groups (p<0.05) for all applications.

• 한국임상약학회지
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• 제25권2호
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• pp.74-79
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• 2015

Objective: Treatment with sulfonylureas in combination with metformin improves glycemic control in type 2 diabetes mellitus (T2DM), but is associated with hypoglycemia and weight gain. This retrospective study aims to compare the effectiveness of dipeptidylpeptidase-4 (DPP-4) inhibitors and sulfonylureas as an add-on therapy to metformin in patients with T2DM. Methods: Data from medical records of 355 T2DM patients received therapy either DPP-4 inhibitors (DPP-4 inhibitor group) or sulfonylurea (SU group) in combination with metformin from 1 March 2009 to 30 September 2011 were retrospectively reviewed. Of total 355 patients, 231 patients were in DPP-4 inhibitor group and 124 patients were in SU group. Baseline Hemoglobin $A_{1c}$ ($HbA_{1c}$) level in SU group was higher than DPP-4 inhibitor group with a statistically significant difference (8.6% vs. 7.8%). Comparative analysis between DPP-4 inhibitor group and SU group was performed for $HbA_{1c}$ values, amounts of $HbA_{1c}$ changes, and rates of $HbA_{1c}$ changes from baseline at 6-month intervals and incidence rates of major cardiocerebral events. Results: SU group showed larger $HbA_{1c}$ changes in both amounts and rates compared to DPP-4 inhibitor group, although statistical significance was not found in all study periods. Proportions of patients with stable $HbA_{1c}$ <6.5% or 7% were significantly higher in DPP-4 inhibitor group than SU group (<6.5%: 30.4% vs. 13.4%, <7%: 72.3% vs. 41.2%). Time to achieve stable $HbA_{1c}$ <6.5% was not significantly different, but time to achieve stable $HbA_{1c}$ <7% was shorter in DPP4 inhibitor group than SU group with a significant difference. The incidence rate of cardiocerebral events in group of patients with or without previous events was 1.7%, not significantly lower than that in DPP-4 inhibitor group (4.0%). For newly encountered cardiocerebral events during the treatment, incidence rates of two groups did not differ significantly. Conclusion: DPP-4 inhibitors were as effective as sulfonylureas in achieving the $HbA_{1c}$ goal of less than 6.5% or 7% and cardiocerebral event rates did not differ between the two drugs.

• 한국임상약학회지
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• 제27권2호
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• pp.99-104
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• 2017

Objectives: This study aimed to compare effects on glycemic control and weight loss between the metformin/dapagliflozin combination and the metformin/sitagliptin combination in type 2 diabetic patients. Methods: This study retrospectively reviewed the medical records, from January $1^{st}$ 2015 to March $31^{st}$ 2016, of type 2 diabetic patients who were older than 18 and were prescribed with dapagliflozin or sitagliptin in combination with metformin. Hemoglobin $A_{1c}$ ($HbA_{1c}$) levels and weights were measured every 3 months. Results: The dapagliflozin group showed a greater decrease in $HbA_{1c}$ levels after 3 months (-0.75% vs. 0.01%, P<0.001), 6 months (-0.36% vs. 0.08%, P=0.029), and 9 months (-0.53% vs. 0.08%, P=0.046) compared to the sitagliptin group. Also, the dapagliflozin group showed a greater significant decrease in the rate of change in $HbA_{1c}$ levels after 3 months (-0.09 vs. 0.01, P<0.001), 6 months (-0.04 vs. 0.01, P=0.031), 9 months (-0.07 vs. 0.02, P=0.029), and 12 months (-0.05 vs. 0.05, P=0.047). Furthermore, the dapagliflozin group showed a greater decrease in amount of weight change after 3 months (-2.46 kg vs. 0.37 kg, P<0.001), 6 months (-3.02 kg vs. 0.13 kg, P<0.001), and 9 months (-2.27 kg vs. 0.50 kg, P=0.002). Finally, the dapagliflozin group showed a greater decrease in the rate of change in weight after 3 months (-3.10% vs. 0.52%, P<0.001), 6 months (-3.83% vs. 0.21%, P<0.001), 9 months (-2.84% vs. 0.79%, P=0.002), and 12 months (-4.91% vs. 0.44%, P<0.001). Conclusions: It was concluded that dapagliflozin is more effective than sitagliptin for type 2 diabetic patients.

• 한국산학기술학회논문지
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• 제21권3호
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• pp.215-222
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• 2020

메트포르민은 제2형 당뇨병의 1차 치료제로 사용되는 약물로 다른 당뇨병 치료제에 비해 투여 용량이 크고 용해도는 높으나 위장관 투과도가 낮은 특성을 갖고 있으며 주로 위장관 상부에서만 흡수되는 이유로 생체이용률이 40~60%로 낮은 편이다. 따라서 본 연구를 통해 위체류 약물전달시스템을 적용하여 제제가 위에 머무르는 시간을 증가시키고 제제로부터 방출된 약물을 서서히 소장으로 이동시킨다면 생체이용률을 증가시킬 수 있을 것으로 기대된다. 팽윤성 시스템은 다른 위체류 약물전달시스템에 비해 안정성이 높아 개발목표기술로 선정하였고, 팽윤성 기제로는 기존의 연구와 다르게 카라기난과 히프로멜로오스를 병용하여 차별성을 확보하였다. 카라기난과 히프로멜로오스 병용 시스템은 각각의 함량이 15/110 질량분율일 때 가장 높은 팽윤성과 적절한 서방성 용출패턴을 나타내었다. 또한 각각의 함량이 15 %와 14 %가 되도록 제조한 메트포르민 정제를 시판 정제와 비교 시 더 우수한 팽윤성이 나타남을 확인하였다. 결론적으로 본 연구 결과에 의해 메트포르민의 서방출을 위한 새로운 팽윤성 위체류 약물전달시스템이 개발되었으며 다양한 주성분에 대한 추가적인 연구가 수행되면 의약품, 화장품, 건강기능식품 등의 분야에서 효과적인 약물전달시스템으로 응용될 수 있을 것으로 기대된다.

• 월간당뇨
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• 통권140호
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• pp.74-75
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• 2001

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2005년도 국제학술대회
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• pp.345-350
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• 2005

Acute toxicities of five pharmaceutical products were evaluated with aquatic microbes, invertebrates, and fish. The test pharmaceuticals, i.e., cimetidine, carbamazepine, diltiazem, acetaminophene, and metformin have been often detected in aquatic environment, but theire cological hazard on receptors of various trophic levels has seldom been evaluated. In the present study, we conducted acute toxicity assays with a marine bacterium, Vibrio fischeri, an invertebrate, Daphnia magna, and a fish, Japanese medake (Oryzias latipes). In general, D. magna, showed the most sensitive response to the test chemicals. Diltiazem exhibited the lowest EC50 value after 96 hr of exposure at 7.6 mg/L, followed by cimetidine >acetaminophen > metformin = carbamazepine in an order of decreasing susceptibility. With the fish, diltiazem and carbamazepine showed the 96 hr EC50 values at 14.1${\sim}$35.4 mg/L while acetaminophen, cimetidine, and metformin did not cause 50% mortality at 100 mg/L. Similar pattern was noted with the Microtox Assay, with which the median effective concentrations for acetaminophen, cimetidine, and metformin were found at the range between 301.8 and 755.4 mg/L. Carbamazepine and diltiazem exposure to the microbes resulted in EC50 values around 50 mg/L. Predicted no effect concentrations (PECs) of these pharmaceuticals derived from the EC5O values obtained from this study, and predicted environmental concentrations (PECs) obtained from available literatures were utilized to estimate ecological risks of the test compounds. No test pharmaceuticals resulted in risk quotients (PEC/PNEC) greater than 1, which suggests no serious potential ecological concerns. It should be noted however that further studies including the refinement of PEC derivation, identification and toxicity assessment of the metabolites and/or their interactions with other stressors may be warranted to better understand the environmental consequences of the residual pharmaceutical discharge to the waterway.