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한규원,정낙신,김길수 梨花女子大學校 藥學硏究所 2000 藥學硏究論文集 Vol.- No.9
In order to assay the efficacy of newly synthesized antiviral compounds, pyrimidine analogs, pharmacokinetics of those were established as compared with already marketed zidovudine. Zidovudine (15, 20, 25 and 35 ㎎/㎏), LJ142 (18.52 ㎎/㎏) and LJ143 (15, 18.52 and 30 ㎎/㎏) were administered orally and intravenously in rats, blood samples were collected post-injection(i.e., for 360 min) at appropriate time intervals. Those were analyzed by HPLC with UV detection at 265 ㎚. Pharmacokinetic parameters (C_max, T_(1/2) MRT, AUC, AUMC, Vd_ss, Cl_t) were calculated. AUCs of zidovudine and LJ143 following I.V. dosing of 15∼25 ㎎/㎏ and 15∼18.18 ㎎/㎏ were dose-independent, However, AUCs of zidovudine and LJ143 following I.V. dosing of 25∼35 ㎎/㎏ and 18.18∼30 ㎎/㎏ were dose-dependent. The relative bioavailability of zidovudine, LJ142 and LJ143 following oral administration were 61.94, 46.44 and 78.24%, respectively.
Zidovudine의 In Vitro 세포내 대사물의 측정을 통한 약효 검색법 개발
한규원,김길수 梨花女子大學校 藥學硏究所 2002 藥學硏究論文集 Vol.- No.11
ln order to assay the efficacy of newly synthesized antiviral compounds, in vitro studies of their active intra-cellular phosphorylated metabolites were established as compared with Zidovudine (ZDV). Antiviral base analogs requireintracellular phosphorylation prior to the inhibition of HIV replication. Therefore, antiviral drugs concentrations in plasmahave not reflected any direct relationship with activity or toxicity. A method has been developed to measure the con-centration of total phosphorylated metabolites inside peripheral blood mononuclear cells using modified comnercial radio-immunoassay (RIA). ZDV 5'-monophosphate was synthesized and used as a procedural control for RIA modification.PBMCs were isolated from whole blood and incubated with ZDV for 2O h to allow metabolic phosphorylation. Vable cellswere extracted overnight with 60% methanol. After evaporation, the extract waa reconstituted in Tris buffer. Samples weresplit into two fractions, one of which was treated with alkaline phosphatase (AP) to liberate phosphate groups. Con-centrations of phosphorylated metabolites were determined by subtracting the concentration of non-AP-treated fraction fromthat of the treated fraction. Recovery of phosphorylated ZDV from cell extracts was approximately 90%, and reproducibilitywas acceptable (coefficients of variation <15% for concentrations≥0.25 ng/mL). Intracellular concentrations (0.135-5.019nmole/10^6 cells) followed a nonlinear dose-response relationship over the range 0.015-2.996mM extracellular ZDY, withconcentration-dependant saturation.
韓奎元 又石大學校 1984 論文集 Vol.6 No.-
Japanese imperialist extremly practised a private school suppression policy under the cloak of realization of their sphere of a Great East Asia mutual prosperity at the end of a colonialism about Korea. So, it practised prohibition and suppression of students activities, expulsion of a school purposely or exacted to convert a private school into public school Especially it exacted worshiping of schrine from mission school