Effects of Guanosine on the Pharmacokinetics of Acriflavine in Rats Following the Administration of a 1:1 Mixture of Acriflavine and Guanosine, a Potential Antitumor Agent

이풍석,신대환,Kyoung Mi Lee,송석길,유환수,문동철,홍진태,정연복 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.3

Preclinical studies are currently underway to examine the potential antitumor effects of a 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine. Guanosine potentiates the anti-cancer activity of some compounds. However, the effects of guanosine on the pharmacokinetics of ACF in mammals are unknown. Therefore, this study investigated the effects of guanosine on the pharmacokinetics of ACF after administering a 1:1 mixture of ACF and guanosine in rats. The rats were given either 10 mg/kg of the mixture or 5 mg/kg ACF via an intravenous bolus injection; or 30 mg/kg of the mixture or 15 mg/kg ACF intramuscularly. An HPLC-based method, which was validated in this laboratory, was used to analyze the levels of trypaflavine (TRF) and proflavine (PRF) in the plasma, bile, urine, and tissue homogenates. It was found that TRF and PRF were rapidly cleared from the blood and transferred to the tissues after the i.v. bolus or i.m. injection of the combination mixture. Both TRF and PRF were found to be most highly concentrated in the kidneys after the i.v. bolus or i.m. injection, followed by slow excretion to the bile or urine. Guanosine had no effect on the plasma disappearance of TRF or PRF after the i.v. bolus injection, However, guanosine led to a prolongation of the plasma levels of PRF after the i.m. administration of the combination mixture, resulting in a2 fold increase in the bioavailability (BA) of PRF. The concentrations of TRF and PRF in all the tissues examined were similar in the groups given the mixture and ACF. However, guanosine led to a prolongation of the biliary and urinary excretions of both TRF and PRF after the i.v.bolus (1.25 fold) or i.m. (1.5-2.4 folds) injection. These prolonged effects of guanosine on the plasma disappearance or urinary excretion of TRF and PRF might be one reason for the enhanced antitumor effects of ACF. However, more study will be needed to further examine this potential mechanism

Kinetic Analysis about the Bidirectional Transport of 1-Anilino-8-naphthalene Sulfonate(ANS) by Isolated Rat Hepatocytes

이풍석,송임숙,TaeHaShin,정석재,심창구,송석길,정연복 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.4

The purpose of the present study was to investigate the bidirectional transport of 1-anilino-8- naphthalene sulfonate (ANS) using isolated rat hepatocytes. The initial uptake rate of ANS by isolated hepatocytes was determined. The uptake process of ANS was saturable, with a Km of 29.1±3.2 mM and Vmax of 2.9±0.1 mmol/min/mg protein. Subsequently, the initial efflux rate of ANS from isolated hepatocytes was determined by resuspending preloaded cells to 3.0% (w/v) BSA buffer. The efflux process for total ANS revealed a little saturability. The mean value of the efflux clearance was 2.2±0.1 mL/min/mg protein. The efflux rate of ANS from hepatocytes was markedly decreased at 4oC, indicating that the apparent efflux of ANS might not be attributed to the release of ANS bound to the cell surface, but to the efflux of ANS from intracellular space. The efflux clearance was furthermore corrected for the unbound intracellular ANS concentration on the basis of its binding parameters to cytosol. The relation between efflux rate and unbound ANS concentration was fitted well to the Michaelis-Menten equation with a saturable and a nonsaturable components. The Vmax and Km values were 0.54 mmol/min/mg protein, and 10.0 mM, respectively. Based on the comparison of the ratios of Vmax to Km (Vmax/Km) corresponding to the transport clearance, the influx clearance was two times higher than the efflux clearance. Together with our preliminary studies that ATP suppression in hepatocytes substantially inhibited ANS influx rate, we concluded that the hepatic uptake of ANS is actively taken up into hepatocytes via the carrier mediated transport system.

북한의 현대전 개념과 7日戰 전략

李風石 세계평화교수협의회 1986 廣場 Vol.154 No.-

흰쥐에서 항암성화합물인 육산화비소의 체내동태

이풍석 ( Pung Sok Lee ),신대환 ( Dae Hwan Shin ),이소영 ( So Young Lee ),이중열 ( Jung Yeol Lee ),이경미 ( Kyoung Mi Lee ),권구현 ( Koo Hyun Kwon ),정연복 ( Youn Bok Chung ) 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.6

피부미백 신약후보물질 Glucose Pentoisovalerate의 경피흘수 및 체내동태

이풍석, 양호현, 김창수, 손표민, 문동철, 정연복 충북대학교 약품자원개발연구소 2004 약학논문집 Vol.19 No.-

-본문참고-

[화학] 넙치에서의 Pefloxacin의 분포에 관한 연구

이풍석(Pungsok Lee),장원철(Woncheoul Jang) 한국분석과학회 1999 분석과학 Vol.12 No.1

MDA를 이용한 다중 에이전트 기반 시스템 개발단계에서 재사용성 향상을 위한 프레임워크

이풍석(Poong-Seok Lee),장수현(Soo-Hyun Jang),이은석(Eun-Seok Lee) 한국정보과학회 2007 한국정보과학회 학술발표논문집 Vol.34 No.2B

최근 유비쿼터스 환경에서 동작하는 지능형 시스템에 관한 관심이 높아지면서, 이러한 지능형 시스템의 개발을 효율적으로 하기 위해 에이전트 기반의 소프트웨어 시스템 개발 방법론 및 지원 도구에 관심이 높아지고 있다. 이러한 시스템들은 에이전트들의 동작환경을 제공하는 에이전트 플랫폼의 사용이 필수적이다. 그러나 실제로 에이전트 기반 시스템을 개발하는 경우 초기 단계에서 가장 적절한 에이전트 플랫폼을 결정하는 것은 어렵다. 또한 개발 중에 다양한 에이전트 플랫폼에 적용 가능한 소프트웨어를 개발해야 하는 경우가 발생할 수 있다. 따라서 본 논문에서는 이러한 문제점을 해결하기 위해 MDA를 기반으로 에이전트 기반 시스템 개발 방법론 및 개발 지원 도구를 제공하고자 한다. 본 논문에서 제안하는 방법을 통해 개발자는 개발 초기 단계에서 결정된 소프트웨어의 아키텍처를 기반으로 다양한 플랫폼에 적용 가능한 에이전트 모델과 소스코드를 생성시킬 수 있다. 본 논문에서는 플랫폼 독립적인 에이전트 모델을 통하여 FIPA-OS와 MTI 에이전트 플랫폼 기반의 소스코드를 생성시키는 실험을 하여 제안 방법론 및 도구의 유효성을 검증한다.

Extensive Hepatic Uptake of Pz-peptide, a Hydrophilic Proline Containing Pentapeptide, into Isolated Hepatocytes Compared with Colonocytes and Caco-2 Cells

TaeHaShin,이풍석,권오승,정윤복 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.1

The objective of the present study was to investigate the uptake process of 4-Phenylazobenzoxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-peptide), a hydrophilic and collagenase-labile pentapeptide, by isolated hepatocytes. For comparison, the uptake of Pz-peptide by Caco-2 cells and colonic cells, two known paracellular routes of Pz-peptide, was also evaluated. A simple and sensitive reversed-phase HPLC assay method using UV detection has been developed. The coefficient of variation for all the criteria of validation were less than 15%. The method was, therefore, considered to be sutable for measuring the concentration of Pz-peptide in the biological cells. Pz-peptide was extensively uptaked into hepatocytes. The initial velocity of Pz-peptide uptake assessed from the initial slope of the curve was plotted as Eadie-Hofstee plots. The maximum velocity ( V max ) and the Michaelis constant ( K m ) were 0.190 ± 0.020 nmol/min/10 6 cells and 12.1 ± 3.23 μ M, respectively. The permeability-surface area product ( PSinflux ) was calculated to be 0.0157 ml/min/10^6cells. V_{max}and K_mvaluesforCaco−2cellswerecalculatedtobe6.22 \pm0.930pmol/min/10 6 cells and 82.8 ± 8.37 μ M, respectively, being comparable with those of colonocytes (6.04 ± 1.03 pmol/min/10^6cellsand87.8 \pm13.2 \muM,respectively). PS_{influx}valuesforCaco−2cellsandcolonocyteswerecalculatedtobe0.0751 \mul/min/10 6 cells and 0.0688 μ l/min/10^6cells,respectively.ThemorepronounceduptakeofPz−peptidebyhepatocytes,whencomparedwithCaco−2cellsandcolonocytes,isprobablyduetoitsspecifictransporter.Inconclusion,Pz−peptide,aparacellularlytransportedpentapeptideintheintestineandocularepithelia,wasuptakedintohepatocytesextensively.AlthoughPz−peptideisabletobeuptakedintotheCaco−2cellsandcolonocytes,itislesspronouncedwhencomparedwithhepatocytes. PS_{influx}$ values of Caco-2 cells and colonocytes for unbound Pz-peptide under linear conditions were less than 0.4% when compared with that of hepatocytes.

Formulation and Evaluation of an Alternative Triglyceride-free Propofol Microemulsion

조재평,조진철,이풍석,이마세,오의철 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.9

A new triglyceride-free propofol microemulsion for intravenous injection was formulated using nonionic surfactants, poloxamers and polyethylene glycol 660 hydroxystearate. The aim of this investigation was to evaluate the formulation for storage stability, antimicrobial activity, toxicity and preclinical efficacy. The results were compared to the characteristics obtained for the most commonly used formulation of propofol (Diprivan®). The mean particle diameter of the microemulsion was less than 100 nm so that it could be readily sterilized using a 0.22 μm membrane at room temperature. The microemulsion formulation demonstrated enhanced stability compared to the marketed macroemulsion formulation. In a stress storage condition, it was physicochemically stable for at least 40 months. This new formulation showed higher antimicrobial activity, lower risk of hyperlipidemia and better tolerability than Diprivan®. In preclinical studies, the efficacy and pharmacokinetic profile of the microemulsion were similar to those of Diprivan®. Nevertheless, the administration of the microemulsion caused considerably low histamine release compared to the macroemulsion. Based on these results, the newly developed microemulsion of propofol appeared to have several advantages and, thus, could be an alternative to the fat macroemulsions of propofol.

Preparation and Stability Evaluation of Docetaxel-Loaded Oral Liposome

전종란,김현미,이풍석,오의철,이마세 한국약제학회 2010 Journal of Pharmaceutical Investigation Vol.40 No.2

Docetaxel-loaded liposomes were prepared by emulsion-solvent evaporation method, then coated with chitosan at room temperature and lyophilized. This system was designed in order to improve solubility and stability of docetaxel in the GI tract for oral drug delivery. The solubilizing effect of some frequently used solubilizers and/or liposome was determined. Among the results docetaxel-loaded liposomes prepared with 0.5% TPGS as a solubilizer showed 100-fold higher solubility than docetaxel. In a stability test, mean particle size of different liposome formulations was measured by a particle size analyzer in simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). The particle size of uncoated liposomes was significantly increased compared with that of chitosan-coated liposomes in SGF, however, there was no significant difference between coated and uncoated liposome in SIF. It is evident that chitosan-coated liposomes were more stable in GI conditions. The release characteristics of docetaxel-loaded liposomes were also investigated in three buffer solutions (pH 1.2, 4.0, 6.8). Docetaxel release did not occur in pH 1.2 for 4 hrs. However, in pH 4.0 and 6.8 conditions, docetaxel was gradually released over 24 hrs as a sustained release. It seems that aggregation and precipitation of particles by electrostatic interaction might protect docetaxel from being released. In Conclusion, the results from this study show that the chitosan-coated liposomes may be useful in enhancing solubility and GI stability of docetaxel.