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내인성 N1- methylnicotinamide 를 이용한 신혈장유량측정
심창구 한국약제학회 1983 Journal of Pharmaceutical Investigation Vol.13 No.1
Renal plasma flow (RPF) was estimated from the extraction ratio (E.R.) and renal plasma clearance of the endogenous N¹-methylnicotinamide(NMN) in the experimental renal failure (ERF) rat, and was compared with that of healthy rats. PRE of ERF-rats was not different from that of the healthy rat significantly and dependened upon E. R, or intrinsic clearance of the kidney. This NMN method seemed to be superior to the conventional p-aminohippuric acid (PAH) method clinically.
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음이온 모델 화합물 아마란스의 담즙배설에 미치는 타우로데옥시콜레이트의 영향
심창구,정석재 한국약제학회 1986 Journal of Pharmaceutical Investigation Vol.16 No.3
Plasma disappearance of amaranth (AM), a model compound of organic anionic drugs, was retarded by intravenous infusion of taurodeoxycholate (TDC), a representative bile acid, in the rat. Biliary excretion accounted for 30-60% of the systemic excretion of AM. AM seemed to be metabolised in the hepatocyte to form a compound that is excreted more rapidly into the bile than AM itself, considering apparent biliary clearance, CL_(bil), is much larger than systemic clearance, CLs. Decrease in CL_(bil) by TDC infusion might be due to elevated plasma level rather than decreased biliary excretion of AM. Decreased distribution or urinary excretion of AM by TDC was supposed to be one of the probable reasons of elevated plasma level. Competitive inhibition between AM and TDC on tissue distribution and urinary excretion might explain the mechanism. The effect of TDC on the CL_(bil) of methylene blue, a cationic dye, was quite different from that of AM, as reported previously by us. More intensive study would be necessary to elucidate the difference of biliary excretion between organic anions and cations.
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실험동물에 정맥주사 및 경피로 투여된 α - 인터페론의 약물체내속도론적 연구
심창구,김대덕,정인환,장욱,김현수,유우영 대한바이러스학회 1985 Journal of Bacteriology and Virology Vol.15 No.1
Abstract-The pharmacokinetic behavior of a-interferon (IFN) was studied in experimental animals (rat or mouse) after intravenous or topical administration. Dissolution of IFN to organic solvent (isopropyl myristate) from polyethyleneglycol ointment together with partition between aqueous phase and organic phase (isopropyl myristate) were also studied to clarify the pharmaceutical characteristics of IFN ointment. Serum concentrations of IFN after I. V. administration to rats were in good agreement with a two-compartment open model. Pharmacokinetic analysis indicates that IFN has small distributions volume (Vdss) and nonrenal clearance explains almost all of total body clearance (CL). Skin tissue concentrations of IFN after topical administration to nude mice could be explained by a one-compartment model with first order absorption. Pharmacokinetic analysis indicates that IFN penetrates rapidly into skin tissues and the concentrations in the tissues are CL limited. Dissolution test and partition experiment indicate that IFN has moderate lipophilicity and polyethyleneglycol is adequate for ointment base because of its moderate compatibility with IFN.
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심창구 한국약제학회 1987 Journal of Pharmaceutical Investigation Vol.17 No.4
Renal dysfunction can have pronounced effects on the pharmacokinetic and phatmacodynamic characteristics of drugs. Because the exploration of these effects in patients may be limited by ethical and practical considerations, it often become necessary to perform studies on animals with experimental renal failure(ERF). ERF was produced in rats by the administration of uranyl nitrate, glycerol, salicylate, gentamicin and folate in this study. Changes in glomerular filtration rate(GFR) and renal secretion clearance of tetraethylammonium bromide(CL^(scn)_(TEA)), together with morphological changes of kidney cortex were evaluated and compared among ERF models. GFR(or glomeruli) and CL^(scn)_(TEA) (or renal tubules) were not damaged parallelly in some ERF model rats. Therefore, it seemed to be necessary to adjust dosage regimen of some basic drugs like TEA in renal dysfunction considering the functional changes of renal secretion in addition to glomerular filtration.
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Pharmacokinetic Study of Recombinant Human Interferon Alpha A in Rats
심창구,김대덕,김현수,정인환,유무영,Shim, Chang-Koo,Kim, Dae-Duk,Kim, Hyun-Su,Jung, In-Whoan,Yoo, Moo-Young Korean Society for Biochemistry and Molecular Biol 1987 한국생화학회지 Vol.20 No.2
Recombinant human interferon-${\alpha}A$ (인터페론)를 rat에 정맥주사한 다음의 혈청 및 뇨중 인터페론 역가를 정량하여 약물체내속도론을 이용하여 해석하였다. 정맥주사시 2가지 $9.0{\times}10^6\;IU/ml$ 및 $3.6{\times}10^7\;IU/ml$)로 다른 용량을 투여하여 보았으나 용량에 따른 속도론 파라메타의 유의성있는 차이 (p>0.05)가 나타나지 않았다. 이로부터 이정도의 용량에서는 체내동태에 용량의존성 (포화과정)이 나타나지 않는 것으로 생각되었다. 이 인터페론의 체내동태는 저자 등이 이미 보고한 바 있는 Namalva 인터페론의 체내동태와 유사하였으나 문헌에 있는 베타인터페론과는 상이하였다. 이 인터페론의 뇨중 배설속도와 혈중농도의 상관관계가 직선성을 보이는 점으로부터 비록 인터페론이 신장에서 여파, 분비, 재흡수 및 분해, 대사라는 복잡한 과정을 거쳐 뇨중에 배설된다. 하지만 이 연구에서와 같은 혈중농도 범위내에서는 각 과정에 포화현상이 나타나지 않았다는 (또는 나타나도 무시할 수 있는 정도라는) 사실을 알 수 있었다. 신클리어란스($CL_r$)가 전신클리어란스($CL_s$)의 0.1%에 불과한 것은 인터페론이 신장에서 상당량 catabolism을 받기 때문이라고 생각된다. Pharmacokinetic behavior of recombinant human interferon alpha rIFN-${\alpha}A$ was studied in the rat. Serum concentrations of rIFN-${\alpha}A$ after intravenous administration could be explained by two - compartment open model. Pharmacokinetic parameters of f recombinant human interferon alpha administered intravenously at two different doses $9.0{\times}10^6$ and $3.6{\times}10^7\;IU/kg$) were calculated by fitting the observed data to the nonlinear least square program. There were no significant differences in pharmacokinetic parameters such as systemic clearance (CLs), apparent distribution volume at steady state ($Vd_{ss}$), biological half life ($t_{1/2}$) etc. between the two doses. There were also no significant differences between pharmacokinetic parameters of this rIFN-${\alpha}A$ and those of Namalva rIFN-$\alpha$ which were reported previously by us. rIFN-${\alpha}A$ aministered intraveneously had a small distribution volume, which indicates its poor distribution to peripheral or poorly-perfused organs. Renal excretion which might be a sum of filtration, secretion, reabsorption or catabolism in the kidney didn't show any saturation phenomena in the serum concentration range studied $1{\times}10^3-5{\times}10^4\;IU/ml$). Renal clearance accounted less than 0.1% of systemic clearance of rIFN-${\alpha}A$.
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