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질산우라늄으로 유발시킨 실험적 급성 신장해에 의한 간장의 안티피린의 대사 기능 저하
김대덕,심창구 ( Dae Duk Kim,Chang Koo Shim ) 생화학분자생물학회 1988 BMB Reports Vol.21 No.1
Effect of acute renal failure (ARF) on the hepatic metabolism of antipyrtine was investigated in the rat. Total body clearance (CL_t) of antipyrine was decreased (40%) significantly (p$lt;0.05) by ARF. ARF did not affect the hepatic plasma flow and tissue distribution of antipyrine. The decrease in CL_t was attributed to the decrease in hepatic intrinsic clearance (CL_(int)) of antipyrine. Therefore, it seems to be noted that hepatic metabolism of drugs is damaged in some ARF models.
질산우라늄으로 유발시킨 실험적 급성 신장해에 의한 간장의 안티피린 대사 기능 저하
김대덕,심창구,Kim, Dae-Duk,Shim, Chang-Koo 생화학분자생물학회 1988 한국생화학회지 Vol.21 No.1
질산우라늄으로 급성신장장해 (acute renal failure:ARF)를 유발시킨 rat에 안티피린을 IV 또는 경구투여하여 혈청중 농도 추이로 부터 전신클리어란스 ($CL_t$)를 계산하였던바, ARF에 의해 각각의 $CL_t$가 약 40% 저하되는 사실을 발견하였다. 이 원인을 규명하고자 간중량, 위장관흡수, 혈구분배, 혈장단백결합, 간혈류, 간 고유클리어란스 ($CL_{int}$)의 변화를 조사하였다. 그 결과 $CL_t$의 40% 감소는 $CL_{int}$의 감소 (48%)로 잘 설명되었다. $CL_{int}$의 감소 기전에 대해서는 보다 깊은 연구가 필요하겠지만 신장에만 선택적으로 장해를 일으키는 것으로 알려져온 우라늄에 의한 ARF를 신장장해 모델로 사용할 때에는 이와 같은 대사 가능의 저하에 유의하지 않으면 안됨이 밝혀졌다. 이 결과는 신장해시의 간대사 기능이 증가 또는 감소한다는 종래의 논의에 대해 유용한 정보를 제공한 것으로 생각된다. Effect of acute renal failure (ARF) on the hepatic metabolism of antipyrtine was investigated in the rat. Total body clearance $(CL_t)$ of antipyrine was decreased (40%) significantly (P<0.05) by ARF. ARF did not affect the hepatic plasma flow and tissue distribution of antipyrine. The decrease in $CL_t$, was attributed to the decrease in hepatic intrinsic clearance ($CL_{int}$) of antipyrine. Therefore, it seems to be noted that hepatic metabolism of drugs is damaged in some ARF models.
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-${\alpha}A$.
심창구,김대덕,정인환,김현수,유무영,Shim, Chang-Koo,Kim, Dae-Duk,Jung, In-Whoan,Kim, Hyun-Su,Yoon, Moo-Yung 한국약제학회 1986 Journal of Pharmaceutical Investigation Vol.16 No.3
Time-concentration curves of recombinant human interferon alpha$(rIFN-{\alpha}A)$ in the skin and serum of nude mice or rats were studied after topical application of IFN ointment. IFN appeared in the skin and serum in less than 30 minutes and lasted for more than 10-12 hours at high concentration level after the application to nude mice at a dose of $9.0{\times}10^5\;IU/g$ mouse. But in the rats, IFN was not detected in the serum even 7 hours after the application at a dose of $6.0{\times}10^5\;IU/g$ rat. Topical application of IFN might be useful for the topical and systemic treatment if the human skin resembles that of nude mouse in respect to transport characteristics.
심창구,김대덕,김현수,정인환,유무영 ( Chang Koo Shim,Dae Duk Kim,Hyun Su Kim,In Whoan Jung,Moo Young Yoo ) 생화학분자생물학회 1987 BMB Reports Vol.20 No.2
Pharmacokinetic behavior of recombinant human interferon alpha (rIFN- α A) was studied in the rat. Serum concentrations of rIFN- α A after intravenous administration could be explained by two - compartment open model. Pharmacokinetic parameters of rIFN- α A administered intravenously at two different doses (9.0 × 10^6 and 3.6 × 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_½) etc. between the two doses. There were also no significant differences between pharmacokinetic parameters of this rIFN- α A and those of Namalva IFN- α which were reported previously by us. rIFN- α 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 × 10³ - 5 × 10⁴ IU/㎖). Renal clearance accounted less than 0.1% of systemic clearance of rIFN- α A.