• Applied Biological Chemistry
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• 제47권2호
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• pp.251-257
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• 2004

식용식물자원으로부터 활성소재를 찾기 위하여 흰씀바귀 뿌리를 80% MeOH로 추출하고, 얻어진 추출물을 EtOAc, n-BuOH및 $H_2O$로 용매 분획하였다. EtOAc와 n-BuOH 분획에 대하여 column chromatography를 반복하여 4종의 화합물을 분리하였다. 각각에 대하여 2D-NMR을 포함한 스펙트럼 데이터의 해석과 문헌 자료를 조사하여 zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\beta}-hydroxyguaian-4(15),\;10(14 )-diene-6,12-olide$ (3), $3-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4)로 구조를 결정하였다. 이들 화합물에 대하여 ACAT(Acyl-CoA: cholesterol acyltransferase), DGAT (diacylglycerol acyltransferase) 및 FPTase(farnesyl-protein transferase)의 활성에 미치는 억제효과를 측정하였다. Compound 1과 Compound 2는 DGAT에 대한 활성억제효과에 있어서 $IC_{50}$ 값이 각각 0.13 mM, 0.10 mM로 나타났고, FPTase에 대하여는 각각 0.15 mM, 0.18 mM로 나타났으며, ACAT에 대하여는 약한 억제 활성을 나타냈다. 따라서 흰씀바귀는 항암 및 항고혈압의 소재 개발에 있어서 유용한 자원으로 활용될 수 있을 것이다.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• Applied Biological Chemistry
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• 제37권3호
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• pp.203-209
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• 1994

$^{14}C-{\alpha}-endosulfan$(100 nM, $41\;{\mu}g$)을 공시어의 각 조직(간, 신장, 소화관) 추출액에 처리하여 대사물질의 생성과 이에 미치는 cofactor의 영향을 시험관내 반응으로 비교한 결과, 105,000 g soluble fraction에서 phase I system에 해당되는 cofactor의 첨가시 공시어의 간 조직에서 가장 높은 대사물질 생성율을 보였고 phase II system에서는 NADPH를 cofactor로 첨가하였을 때 간과 신장조직에서 높은 대사물질 생성율을 보였다. 하지만 소화관 조직에서는 GSH 단독처리나 GSH+NADPH의 혼합처리시 높은 대사물질 생성율을 보였다. 또한 microsomal fraction에서는 phase I system에 해당되는 cofactor의 첨가시 공시어의 소화관 조직에서, phase II system의 경우 NADPH 단독처리나 NADPH+GSH 혼합처리시 대사물질의 생성이 가장 많았다. 이러한 결과로 보아 공시어의 간과 신장에서는 MFO에 의한 대사작용이, 소화관에서는 GST에 의한 대사작용이 활발하다고 할 수 있었다. 공시어의 각 조직에서 높은 생성율을 보인 대사물질은 EA(endosulfan alcohol), EE(endosulfan ether), EHE(endosulfan hydroxyether)이었으며 in vivo 시험에서와 마찬가지로 endosulfan sulfate는 검출되지 않았다. 이 실험에서 ${\alpha}-endosulfan$은 잉어체내에서 ${\beta}-endosulfan$으로 이성화되었다가 EA로 가수분해되거나 직접 EA로 가수분해되어 다시 EE나 EHE로 산화되며 EHE는 EL(endosulfan lactone)로 산화되는 것으로 제안할 수 있었다.