• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.295-301
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• 2005

Famciclovir is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, $Famvir^{TM}$ tablet 250 mg (Novartis Korea Ltd.) and Famcivir (Hanmi Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, $24.19{\pm}2.08$ years in age and $71.55{\pm}6.89$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 250 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at water. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Famvir^{TM}$ tablet 250 mg, were -2.93, -8.02 and 10.47% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8 to log1.25 (e.g., $log0.92{\sim}log1.01$ and $log0.85{\sim}log1.00$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir was bioequivalent to $Famvir^{TM}$ tablet 250 mg.

• Journal of Pharmaceutical Investigation
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• 제38권3호
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• pp.199-205
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• 2008

Famciclovir, 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine, is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, Famvir tablet 750 mg (Novartis Korea Ltd.) and Famcivir tablet 750 mg (Hanmi Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, $23.38{\pm}1.72$ years in age and $68.59{\pm}7.84\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 750 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations ere similar at water. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Famvir^{(R)}$ tablet 750 mg, were -0.53%, 1.12% and -24.82% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log\;0.9569{\sim}log\;1.0423$ and $log\;0.8763{\sim}log\;1.2136$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir tablet 750 mg was bioequivalent to Famvir tablet 750 mg.

• Journal of Animal Science and Technology
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• 제44권4호
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• pp.483-490
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• 2002

본 논문에서는 카제인 가수분해물의 in vivo 상에서 혈압강하 효과를 알아보고, 혈압강하 기능을 갖는 기능성 펩타이드로서의 활용 가능성을 검토하기 위하여 안전성 검사를 실시하였다. 카제인 가수분해물의 소화관 단백질 분해효소 (펩신, 트립신, 카이모트립신) 내성 시험 결과 카제인 가수분해물은 소화관 효소 처리에 의하여 ACE 저해효과에 차이가 없었으며, 자연발증고혈압쥐를 이용한 혈압강하 실험에서 500 mg/kg을 경구 투여한 결과 12.9% (－28.88 mmHg, P<0.05) 저하하였고, 이들 가수분해물을 30% 난황으로 유화할 경우 15.9% (－30.76 mmHg, P<0.01)의 혈압이 감소하여 난황으로 유화에 의해 다소 혈압강화 효과가 증가하였다. 장기 투여에 의한 혈압강하 효과에서 35일 부터 수축기혈압 감소효과가 나타났으며 12.46% (P<0.05) 감소하였다. 가수분해물의 장기투여에 의한 자연발증고혈압쥐의 체중변화는 대조구와 비교하여 차이가 없었다. 혈압강하 효과를 가지는 카제인 가수분해물의 안전성을 조사한 결과 간장장애 지표로서 사용되는 GOT, GPT 활성에 차이가 없었다. 간장 비대 등의 장기 비대 현상도 없었고 조직병리학적 검사에서도 차이가 없었다. ACE 저해활성을 가지는 카제인 가수분해물은 혈압강하제와 비교하였을 때 비교적 낮은 활성을 나타내지만 항상 섭취하는 식품 중에 존재한다는 점에서 그 유용성이 기대되며, 고혈압 예방을 위한 기능성 식품이나 의약품으로서 개발하기 위해서 앞으로 ACE 저해 펩타이드에 대한 체계적인 안전성 검사가 이루어져야 할 것으로 생각된다.

• Journal of Nutrition and Health
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• 제25권6호
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• pp.429-449
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• 1992

The consumption of foods rich in TDF should not be associated with impaired mineral absorp-tion and long-term mineral status. In surveys of populations consuming high amounts of TDF e.g Third World populations and vegetarinas gross deficiencies in mineral nutrition have not been noted. If mineral status is low among these groups it is most likely caused by the inadequacy or imbalance of the diet and not by the TDF. The key word is interaction which should be inte-rpreted in dietary imbalances that produce nut-rient deficiencies. There are no strong data to support the concept that TDF inhibits mineral absorption through a binding chelation mechanism. Limited data sug-gest that positively charged groups on polymers such as chitosan and cholestyramine will decrease iron absorption in humans and animals. Because TDF does not contain positively charged groups future research should be directed at the possible role of protein consumed along with TDF and the combination of effects on mineral nutrition Phytic acid is acknowledged as a potent chela-tor of zinc. However its association with zinc and its propensity to lower Zn bioavaiability may enhance the absorption of other elements notably copper and iron. The importance of interactions among nutrients including TDF will gain addi-tional attention in the scientific community. Soluble and insoluble dietary fiber function di-fferently in the intestine. Insoluble fibers accele-rate movement through the intestine. Soluble die-tary fibers appear to regulated blood concentra-tions of glucose and cholesterol albeit by some unknown mechanism. In creased viscosity produ-ced by the SDF in the intestine may provide an explanation of how this class of polymers affects plasma glucose cholesterol and other nutrients. Employing a double-perfusion technique in the rat we demonstrated that viscosity produced by SDF will delay transfer of zinc into the circulatory system. This delayed absorption should not be interpreted as decreased utilization. A great deal of additional research is required to prove the importance of luminaly viscosity produced by SDF on slowing nutrient absorption or regulating bllod nutrient homeostasis. Increased intake of TDF in the total human diet appears desirable. A dietary intake of 35g/day should not be considered to have a negative effect on mineral absorption. It is important to educate people that an intake of more than 35g TDF/day may cause an imbalance in the diet that can adve-rsely affect mineral utilization. Acknowledgments. Appreciation is given to Dr. George V. Vahouny(deceased) who was intense a great competitor in and out of science and who gave the author inspiration Portions of this work were supported by the University of Missouri Ag-ricultural Station and by a grant from the Univer-rch Support Grant RR 07053 from the National Institutes of Health. Contribution of the Missouri Agriculatural Experiments Station Journal Series No. 10747.

• Nutrition Research and Practice
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• 제9권2호
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• pp.165-173
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• 2015

BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age $29.5{\pm}5.9years$, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.

• Asian-Australasian Journal of Animal Sciences
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• 제12권3호
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• pp.395-399
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• 1999

Three experiments were conducted to determine the effects of conditioning a complex (20% whey, 10% lactose, 4% plasma protein, 4% wheat gluten and 2% blood meal) diet on growth performance of weanling pigs. In Exp. 1,180 pigs (average initial BW of 6.4 kg) were fed the experimental diet (1.7% lysine) during a 7-d growth assay. Treatments were a meal control (M), standard (ST), and expander (EX) conditioned mash or pellets. Rate and efficiency of gain were decreased by 39% and 21% (p<0.005) respectively, for pigs fed EX diets compared to those fed the ST diet. In Exp. 2,196 pigs (average initial BW of 6.5 kg) were used to determine the effects of EX operating conditions on nutritional value of a pelleted complex diet. When steam conditioning temperature (prior to expanding) was $54^{\circ}C$, increasing cone pressure of the EX from 0 to 7 to 14 kg/cm2 resulted in linear decreases in rate of gain of weaned pigs (p<0.006), suggesting heat damage of the diet. Increasing conditioning temperature (i.e., adding steam) of the diets from 46 to 54 to $63^{\circ}C$ (cone pressure at $12kg/cm^2$) resulted in improved rate of gain (p<0.04) of the pigs. However, none of the pigs fed expanded diets compared favorably to the pigs fed the conditioned $(54^{\circ}C)$ pellets processed with no cone pressure. In Exp. 3,168 pigs (average initial BW of 6.6 kg) were used to determine the effects of expanding the various components of the diet. Treatments were M and ST pellets as controls, EX-corn, EX-corn soybean-meal, EX corn-soybean meal-oil, and EX-complete diet. Efficiency of gain was increased by 13% with EX portions of the diet compared to the mash control, but there was a marked decrease in performance when the complete diet was expanded (p<0.001). Expanded corn-soybean meal-oil supported the greatest ADG with a 19% increase compared to the average of the EX corn and EX corn-soybean meal treatments (p<0.005). In conclusion, our results suggest no benefit from expanding complete phase-I diets.

• Journal of Nutrition and Health
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• 제39권7호
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• pp.599-609
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• 2006

In this study, we investigated the in vivo effect by intake of the irradiated foods such as mackerel and sesame seed which are high in unsaturated fatty acid through TBARS (thiobarbituric acid reactive subtance) and the tissue pathological and genotoxicological test. Thirty two ICR mice are divided into four groups, one non-irradiated (control) group and three irradiated (5, 10, 20 kGy, respectively) groups. Sesame seed and pulverized mackerel in modified AIN93M diet were mixed together then divided into four identical parts. Three parts of them were irradiated by doses of 5, 10, and 20 kGy. These experimental diet were fed to each group for 4, 8 and] 6 weeks. The results of the study were as follows: No significant differences in weight gain were found in each group. Peroxide value of the irradiated diet was higher than that of the non-radiated one and also increased according to the storage period. TBA values in plasma, liver, kidney and Peyer's patch were not significantly different among 4 groups. DNA% in tail, tail length (TL) and tail moment (TM) values of the blood lymphocyte in 4, 8 and 16 week groups and the liver in 16 week group were much measured over the control DNA % in tail of kidney of 8 week group was significantly than the control and TL and TM of 8 week and TM of 16 week groups showed a tendency of higher values. By Peyer's DNA % in tail of 8 week group, DNA % in tail and TM of 16 week groups increased significantly over the control, Ultrastructural examination shows myeline figures and swollen mitochondria in parietal cells and intestinal epithelial cells of 8 and 16 weeks groups. After this study, we need further investigations on the safety of highly consumed foods which contain high contents of unsaturated fatty acid, largely imported and which are possible to be irradiated.

• Nutrition Research and Practice
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• 제12권5호
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• pp.371-377
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• 2018

BACKGROUND/OBJECTIVES: Elevation of postprandial lipemia characterized by a rise in triglyceride (TG)-rich lipoproteins can increase the risk of atherogenesis. The objective of this study was to investigate postprandial lipemia response to a single dietary fat/sugar load test and monitor beneficial changes induced by the consumption of Platycodi radix (AP) beverage in healthy subjects. SUBJECTS/METHODS: A total of 52 subjects were randomly assigned to either placebo or AP beverage group with a high-fat shake in a randomized controlled crossover trial. Postprandial blood was collected at 0, 1, 2, 4, and 6 h and analyzed for TG and lipoprotein lipase mass. Inhibition of pancreatic lipase was determined in vitro. RESULTS: AP inhibited pancreatic lipase activity in vitro ($IC_{50}=5mg/mL$). Compared to placebo beverage, AP beverage consumption with a high-fat shake induced significant increase of plasma lipoprotein lipase mass (P = 0.0111, ${\beta}$ estimate = 4.2948) with significant reduction in very low-density lipoprotein (VLDL) TG concentration (P = 0.038, ${\beta}$ estimate = -52.69) at 6 h. Based on significant correlation between high-fat dietary scores MEDFICTS and postprandial TG responses in VLDL (P = 0.0395, r = 0.2127), subgroup analysis revealed that 6 h-postprandial VLDL TG response was significantly decreased by AP consumption in subjects with MEDFICTS ${\geq}40$ (P = 0.0291, ${\beta}$ estimate = -7214). CONCLUSIONS: AP beverage might have potential to alleviate postprandial lipemia through inhibiting pancreatic lipase activity and elevating lipoprotein lipase mass. Subgroup analysis revealed that subjects with high-fat dietary pattern could be classified as responders to AP beverage among all subjects.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.449-454
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• 2009

5'-AMP-activated protein kinase (AMPK) is a heterotrimeric complex consisting of a catalytic ($\alpha$) and two regulatory ($\beta$ and $\gamma$) subunits. Two isoforms are known for catalytic subunit (${\alpha}1$, ${\alpha}2$) and are encoded by different genes. To assess the metabolic effects of $AMPK{\alpha}1$, we examined the effects of overexpression of adenoviral-mediated $AMPK{\alpha}1$ in hyperlipidemic type 2 diabetic rats. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an established animal model of type 2 diabetes that exhibits chronic and slowly progressive hyperglycemia and hyperlipidemia. Thirty five-week-old overt type 2 diabetic rats (n=10) were administered intravenously with Ad.$AMPK{\alpha}1$. AMPK activity was measured by phosphorylation of acetyl CoA carboxlyase (ACC). To investigate the changes of gene expression related glucose and lipid metabolism, quantitative real-time PCR was performed with liver tissues. Overexpression of $AMPK{\alpha}1$ showed that blood glucose concentration was decreased but that glucose tolerance was not completely recovered on 7th day after treatment. Plasma triglyceride concentration was decreased slightly, and hepatic triglyceride content was markedly reduced by decreasing expression of hepatic lipogenic genes. Overexpression of $AMPK{\alpha}1$ markedly improved hepatic steatosis and it may have effective role for improving hepatic lipid metabolism in hyperlipidemic state.

• Archives of Pharmacal Research
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• 제26권3호
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• pp.224-231
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• 2003

The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.