• Archives of Pharmacal Research
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• 제27권7호
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

• 분석과학
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• 제34권5호
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• pp.193-201
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• 2021

We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r² of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

• 대한수의학회지
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• 제58권4호
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• pp.183-192
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• 2018

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320-400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.

• 동의생리병리학회지
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• 제34권4호
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• pp.184-190
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• 2020

This study was performed to find antibacterial substances contained in Scutellariae Radix (SR) using a systems pharmacological analysis method and to establish an effective strategy for the prevention and treatment of infectious diseases. Analysis of the main active ingredients of SR was performed using Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. 36 active compounds were screened by the parameter values of Drug-Likeness (DL), Oral Bioavailability (OB), and Caco-2 permeability (Caco-2), which were based on the drug absorption, distribution, metabolism, and excretion indicators. The UniProt database was used to obtain information on 159 genes associated with active compounds. The main active compounds with antibacterial effects were wogonin, β-sitosterol, baicalein, acacetin and oroxylin-A. Target proteins associated with the antibacterial action were chemokine ligand 2, interleukin-6, tumor necrosis factor, caspase-8,9 and mitogen-activated protein kinase 14. In the future, systems pharmacological analysis of traditional medicine will be able to make it easy to find the important mechanism of action of active substances present in natural medicines and to optimize the efficacy of medicinal effects for combinations of major ingredients to help treat certain diseases.

• Genomics & Informatics
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• 제20권3호
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• pp.33.1-33.17
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• 2022

Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.

• Journal of Veterinary Science
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• 제21권3호
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• pp.35.1-35.11
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• 2020

Background: Despite common use of tylosin in turkeys, the pharmacokinetic (PK) data for this drug in turkeys is limited. Within a few months of growth, PK of drugs in turkeys undergoes changes that may decrease their efficacy due to variable internal exposure. Objectives: The objective of this study was to investigate the influence of age on the PK of a single intravenous (i.v.) and oral administration of tylosin to turkeys at a dose of 10 and 50 mg/kg, respectively. Methods: Plasma drug concentrations were measured using high-performance liquid chromatography with UV detection. The PK parameters were assessed by means of non-compartmental approach and were subjected to allometric analysis. Results: During a 2.5-month-long period of growth from 1.4 to 14.7 kg, the median value for area under the concentration-time curve after i.v. administration increased from 2.61 to 7.15 mg × h/L and the body clearance decreased from a median of 3.81 to 1.42 L/h/kg. Over the same time, the median elimination half-life increased from 1.03 to 2.96 h. For the oral administration a similar trend was noted but the differences were less pronounced. Bioavailability was variable (5.76%-21.59%) and age-independent. For both routes, the plasma concentration of the major tylosin metabolite, tylosin D, was minimal. Protein binding was age-independent and did not exceed 50%. Allometric analysis indicated a relatively poor predictivity of clearance, volume of distribution and elimination half-life for tylosin in turkeys. Conclusions: Age has a significant impact on tylosin PK in turkeys and dosage adjustment may be needed, particularly in young individuals.

• Fisheries and Aquatic Sciences
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• 제26권2호
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• pp.133-144
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• 2023

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC₅₀) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

• 한국식품위생안전성학회지
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• 제27권3호
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• pp.312-316
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• 2012

본 연구는 국내에서 냉장보관창고 온도에 대한 조사를 수행하여, 온도분포를 추정하였고, 이를 미생물 위해평가의 입력변수로 활용할 수 있도록 적정 확률분포 모델을 제시하였다. 국내 냉장보관창고의 온도분포는 최저 $-3.2^{\circ}C$, 최대 $14.9^{\circ}C$, 평균 $2.55{\pm}3.55^{\circ}C$로 나타났고, $10^{\circ}C$이상 비율은 2.5%로 나타났으며, 대부분의 냉장창고 온도는 설정온도보다 높은 것으로 나타났다. 공간 위치별 온도분포는 상단(2.4~4 m) $0.8{\pm}1.69^{\circ}C$, 중단(1.5~2.4 m) $0.59{\pm}1.68^{\circ}C$, 하단(0.7~1.5 m) $0.65{\pm}1.46^{\circ}C$로 중단 온도가 가장 낮았으며, 위치별 온도차이는 최대 $1.11^{\circ}C$로 공간상에서 온도가 일정하게 유지되는 것이 아니라 어느 정도의 편차가 존재하는 것으로 나타났다. 이상의 수집된 온도자료는 @RISK 를 이용, 적합성 검정(GOF: K-S와 A-D test)을 수행하여, MRA에서 활용할 수 있는 국내 냉장창고 온도분포에 대한 가장 적합한 확률분포모델로 LogLogistic(-4.189, 5.9098, 3.2565)을 선정하였다.

• 한국식품위생안전성학회지
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• 제27권4호
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• pp.366-374
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• 2012

최근 2010년 우리나라 통계에서 가장 문제가 되고 있는 최다 발생 식중독으로 노로바이러스 식중독이 31건, 1994명 환자, 병원성 대장균이 28건, 1926명의 환자가 발생하였다. 세균성 식중독인 병원성 대장균의 특성을 살펴보기 위하여 본 연구에서는 우리나라에서 2009년, 2010년 작성된 병원성대장균 역학조사 보고서에 수록된 68건의 병원성 대장균 식중독의 정보를 수집, 리뷰, 분석하여 우리나라 병원성 대장균의 특성을 파악하고자 하였다. 병원성 대장균 식중독은 급식(64.8%) 및 외식(25.5%)에서 발생률이 약 90%에 해당하였다. 우리나라 발생 병원성 대장균 식중독 원인균의 대부분은 EPEC가 44.7%과 ETEC가 34.2%를 차지하여 이들이 전체의 78.9% 가량 대다수를 차지하였고 EAEC와 EHEC는 각각 10.5와 9.2%에 해당하였다. 전체 68건 사례 중에서 이들이 단일균으로 규명된 것이 모두 59건, 두 가지 타입이 혼재된 건이 8건, 그리고 최종 균의 타입이 동정되지 못한 건수가 1건 있어 오염경로 추적의 어려움을 알 수 있었다. 섭취인구에 따라 다양한 질병 발생률을 보여 평균적으로 $33.6{\pm}30.5%$의 발생률을 나타냈고 주 증상은 설사, 복통, 구토, 발열이 대부분이었다. 식품에서 병원성 대장균이 검출된 사례는 두건으로 햄버거를 섭취한 경우 냉동햄버거 패티에서 병원성 대장균이 검출된 사례와 급식에서 오징어야채무침에서 검출된 건수가 있어서 식품에서 검출률이 낮았지만 쇠고기와 수산물 혹은 야채류에서 관리가 필요함을 알 수 있었다. 식품에서 병원성 대장균 검출이 어렵게 되는 원인으로 분석된 것은 식중독 발생에서 신고까지 지연 (7일 이상 소요된 건수가 14.6-18.5%), 원인 식품 수거 어려움 (음식점에서 식중독 때 섭취 식품 수거율 17.6%)과 같이 제도적 부분에서 개선이 필요하며 이들 주요 애로 사항이외에도 역학 조사반의 어려움으로는 발생기관과 환자의 비협조 및 환자들 샘플채취 미흡, 대조군 확보의 어려움, 유전자 분석의 보완과 같은 부분으로 나타났다. 결론적으로 우리나라 병원성 대장균 식중독은 서구국가와 같이 EHEC과 같은 부분이 아니라 급식 및 외식시설에서 EPEC, ETEC가 주요 원인균인 만큼 향후 대응도 원인균 유입경로 추적 및 분석기술 개발, 역학조사의 제도적 보완과 범 정부부처간의 시스템적인 지원이 필요하다.

• 한국식품과학회지
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• 제35권5호
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• pp.803-811
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• 2003

본 연구에서는 조기류 성분의 유통저장품의 이화학적 변화와 조기류의 황색색소 및 착색용 황색색소의 이화학적 특성 및 유통저장조건에 따른 이화학적 변화를 규명하고자 하였다. 우선 각 인공색소의 저장조건에 따른 연구결과 황색색소와 적색색소의 최대흡수 파장을 UV/Vis spectrometer로 측정한 결과 적색색소는 504 nm, 황색색소는 412 nm에서 최대흡수 파장을 나타내었으며, 황색색소는 산성, 중성, 염기성의 조건과 온도변화에 상당히 안정한 것으로 나타났으나, 적색색소는 산성과 중성의 조건에서는 온도의 변화에 대해서는 안정하였으나 고온의 염기성 물질에서는 상당히 불안정함을 나타내었다. 황색색소와 적색색소의 인공조명에 의한 영향은 광을 차단하여 보관한 경우 색소의 잔존율에 거의 변화가 없었으나 인공광에 의한 손실이 큰 것으로 나타났다. 저장기간 중의 일반성분 중 수분함량은 완만한 감소를 나타냈고 이에 따라 지방이나 단백질, 회분은 약간 증가하는 경향을 보였다. 참조기와 위화된 조기의 색도변화실험에서 참조기의 색소가 불안정한 것으로 나타났다. 이 조기류들의 색소 용출실험에서 $100^{\circ}C$에서 색소의 용출정도가 큰 것으로 나타났으며 이러한 경향은 보든 위화색소에서 유사한 경향을 보여 위화조기의 판별에 이용될 수 있을 것으로 판단되었다. 그리고 착색 변조된 조기의 육안을 통한 판별실험 결과 위화시 육안 판별이 어렵다는 결론을 얻을 수 있었다.