• Archives of Pharmacal Research
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• 제26권11호
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• pp.979-983
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• 2003

The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 $\mu$g/mL$.$h for mild renal failure and 4074 $\mu$g/mL$.$h for moderate renal failure) than that in normal rabbits (i.e., 2295 $\mu$g/mL$.$h). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 $h^{-1}$) than that in normal rabbits (i.e., 0.044 $h^{-1}$ ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.

• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.107-112
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• 2000

The changes in pharmacokinetic parameters of tolbutamide, such as the area under the plasma concentration-time curve from time zero to time infinity (AUC) and elimination rate constant (Kel) were evaluated after oral administration of the drug to rabbits with acute and chronic alloxan-induced diabetes mellitus (AIDRs). After oral administration, the plasma concentrations of tolbutamide were significantly higher between 9 and 12 hr in chronic AIDRs compared with these in control rabbits. Therefore, the AUC was significantly greater in chronic AIDRs $(3,490{\pm}649\;versus\;5,020{\pm}1,030{\mu}gml{\cdot}hr)$. This could be due to inhibition of tolbutamide metabolism by liver in AIDRs since tolbutamide is essentially completely metabolized in liver. Impaired liver and kidney function in AIDRs were based on blood chemistry and tissue microscopy. The absorption rate constant and Kel were significantly slower in chronic AIDRs compared with those in control rabbits.

• 약학회지
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• 제36권6호
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• pp.518-528
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• 1992

To determine the optimal conformation of sulfonylureas, the correlation between conformation and hypoglycemic activity of the two sulfonylureas of tolbutamide and chlorpropamide as hypoglycemic agent was studied using an empirical potential function (ECEPP/2) and the hydration shell model in the unhydrated and hydrated states. The conformational energy was minimized from several starting conformations with possible torsion angles in each molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecules in aqueous solution, the contribution of water-accessible volume of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of two sulfonylureas, it could be suggested that the hydration of sulfonylurea moiety is related to increase the hypoglycemic activity. From the calculation results, it was known that the conformational entropy is the major contribution to stabilize the low-free-energy conformations of two sulfonylureas in unhydrated state. Whereas, in hydrated state, the hydration free energy largely contributes to the total free energies of low-free-energy conformations of tolbutamide and conformational entropy contributes to stabilize the low-free-energy conformations of chlorpropamide. The torsion angles from phenyl ring to urea moiety of the low-free-energy conformations of the two sulfonylureas were shown the nearly regular trend. On the basis of these results, the conformation exhibiting the optimal hypoglycemic activity of sulfonylureas and the binding direction to pancreatic receptor site A could be predicted. Also, according to the side chain lengthening of urea moiety, tolbutamide showed various conformational change. Therefore, steric effect may be important factor in the interaction between sulfonylureas and the putative pancreatic receptor.

• Preventive Nutrition and Food Science
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• 제18권3호
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• pp.169-174
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• 2013

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is "Black Onion Extract") were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyperglycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product "Black Onion Extract" may possess antihyperglycemic potential in diabetes.

• 멤브레인
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• 제23권4호
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• pp.297-303
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• 2013

혈액 속의 글루코우즈의 농도를 측정하기 위해 포스파젠 고분자로 만들어진 진단막을 제조하였다. 혈액 속에 존재할 가능성이 있는 장애성분들이 글루코우즈의 농도측정에 미치는 영향을 조사하였다. 그러한 물질들 중, ascorbic acid (AA)는 기준 플라즈마 용액보다 3~9% 정도 높은 K/S 결과치를 나타내었고, tolbutamide (TA)는 기준용액보다 11~13% 정도 낮은 K/S 결과치를 나타내었고, triglycerides와 bovine serum albumin (BSA)은 기준용액 보다 20~25% 정도 낮은 K/S 결과치를 나타내었다. 그러나 위의 물질들을 제외하고는 대부분의 장애성분들이 포스파젠 고분자 진단막을 이용한 혈당측정에 큰 영향을 미치지 않는다는 것을 보여 주었다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.219-219
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• 2002

The SPP003 is a mixture of water extract from Schizandrae Fructus, Poligoni multiflori Radix, Ginseng Radix Akba and Hoelen. The aim of this study was to investigate the anti-hyperglycemic effect of SPP003 in normal and streptozotocin (STZ)-induced diabetic rats, and to monitor the toxicity of SPP003. Oral glucose tolerance test (OGTT) was performed after oral administration of SPP003 100, 300, 600 and 900 mg/kg in normal rats. Blood glucese concentration was measured at -30 min (vehicle, SPP003 or tolbutamide 60 mg/kg, 0 min (glucose treatment), 60, 120 and 180 min. Rats were administerd STZ 65mg/kg (0.1M citrate buffer, pH 4.5) intraperitoneally to induce diabetes and administered vehicle, Spp003 (100, 300 and 600 mg/kg) or tolbutamide (60 mg/kg) orally once a day for 4 weeks. Blood glucose level was measured a 0, 4, 7, 14, 21 and 29 day after initial drug administration. A single oral toxicity of SPP003 was studied in Sprague-Dawley rats of both sexes. In this study, rats were administered with doses of 1, 2 and 5 g/kg of SPP003. In glucose tolerance test, SPP003 900 mg/kg markedly decreased glucose concentration at 1 hr after glucose treatment. Blood glucose levels were much higher in STZ-diabetic rats. These increases were significantly attenuated by SPP003 600 mg/kg. SPP003 did not show any signigicant toxicity. These findings suggest that SPP003 has hypoglycemic properties in STZ-diabetic rats.

• Toxicological Research
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• 제22권1호
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• pp.1-8
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• 2006

The primary metabolism of pyribenzoxim was studied in rat liver microsomes in order to identify the cytochrome P450 (CYP) isoform(s) and esterases involved in the metabolism of pyribenzoxim. Chemical inhibition using CYP isoform-selective inhibitors such as ${\alpha}$-naphthoflavone, tolbutamide, quinine, chlorzoxazone, troleandomycin, and undecynoic acid indicated that CYP1A and CYP2D are responsible for the oxidative metabolism of pyribenzoxim. And inhibitory studies using eserine, bis-nitrophenol phosphate, dibucaine, and mercuric chloride indicated pyribenzoxim hydrolysis involved in microsomal carboxylesterases containing an SH group (cysteine) at the active center.

• Natural Product Sciences
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• 제7권4호
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• pp.107-109
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• 2001

To investigate anti-diabetic component from the node of lotus rhizome (Nelumbo nucifera; Nymphaeaceae), activity guided isolation was conducted. One amino acid was isolated from active fraction of the aqueous methanolic extract. The structure of this compound was identified as tryptophan (1) by the analysis of spectroscopic evidences and comparisons with the data of authentic samples. Tryptophan reduced the blood glucose level significantly in glucose-fed hyperglycemic mice compared with glucose-treated group and exhibited 44.3% of activity compared with tolbutamide,.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.198-198
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• 2001

No report has been addressed to the CYP isoforms catalyzing chlorpropamide, a structural analogue of tolbutamide. To evaluate enzyme(s) mediating formation of 2-hydroxycWorpropamide, a major metabolite and identified by LC/Mass and NMR, incubation studies using human liver microsomes and cDNA expressed CYP were performed on the presence or absence of selective inhibitors of each CYP isoform. (omitted)

• 생명과학회지
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• 제27권11호
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• pp.1269-1275
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• 2017

최근 들어 곤충을 식품 및 바이오 소재로 이용한 연구가 활발히 진행되고 있다. 그러나 곤충을 이용한 모발 성장 효과에 대한 연구는 아직 미흡한 실정이다. 따라서 본 연구에서는 탈모 예방 및 모발 성장 효과를 가진 새로운 천연물 소재 개발을 위해 갈색거저리 유충 추출물의 항산화 활성 및 모발 성장 촉진 효과를 연구하였다. 갈색거저리 유충 추출물의 항산화 활성 평가를 위해서 DPPH 라디칼 및 아질산염 소거능을 측정하였다. 모발 성장촉진 효과를 측정하기 위해서는 인간 모유두세포(human dermal papilla cell)와 섬유아세포(fibroblast, NIH3T3 cell)를 이용하였으며 MTS assay를 통해 세포생존율 및 세포증식률을 측정하였다. 모유두세포에서 dihydrotesteone (DHT)에 의한 세포사 억제 효과를 확인하였으며, 섬유아세포에서는 tolbutamide (TBM)의 potassium channel blocker 역할에 의한 세포사 억제 효과를 확인하였다. DPPH radical 및 아질산염 소거능 측정 결과 갈색거저리 유충 추출물은 항산화 역할이 뛰어난 것으로 보고된 블루베리와 유사하거나 높은 정도의 항산화능을 가지는 것으로 확인되었다. In vitro 상에서 갈색거저리 유충 추출물을 48시간 동안 처리한 경우, 모유두세포와 섬유아세포의 세포증식을 218% 및 116%까지 증가시켰다. 또한, 모유두세포에서 DHT 처리에 의한 세포사가 갈색거저리 유충 추출물에 의해 억제되는 것을 확인하였으며, 섬유아세포에서는 potassium channel blocker인 TBM에 의해 세포생존율이 감소하였으나 갈색거저리 유충 추출물 처리 시 세포생존율이 정상군과 비슷한 정도로 회복되는 것을 확인하였다. 이상의 결과로부터 갈색거저리 유충 추출물을 이용한 모발성장 및 탈모방지 기능성 소재 개발 가능성을 확인하였다.