• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.335-342
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• 2008

The bioequivalence of two carbamazepine preparations was conducted. The in vivo bioequivalence study in 20 healthy male Korean volunteers was designed by using a single dose, randomized, 2-period crossover with a 3-weeks washout period between the doses. Prior to the in vivo study, an in vitro comparative dissolution test was performed by the paddle and basket method as described in the bioequivalence guidance of the Korea Food and Drug Administration (KFDA). Based on the similar dissolution pattern between two preparations in the dissolution test, the two formulations are demonstrated to be pharmaceutically equivalent. In addition, in vivo bioequivalence test was used to reconfirm the in vitro dissolution results. In the in vivo bioequivalence study, the plasma concentrations of carbamazepine up to 144 h after the administration were determined using a validated HPLC method with UV detection and the bioequivalence between the two drug products was assessed by statistical analysis of the log transformed mean ratios of $C_{max}$, $AUC_{0-t}$ and $AUC_{0-\infty}$. The mean maximum concentration ($C_{max}$) of the test and reference were found to be $1467.0{\pm}335.8\;ng/mL$ and $1465.9{\pm}310.3\;ng/mL$, respectively. The 90% confidence intervals (C.I.) of $C_{max}$ were in the range from 0.95 to 1.05. As for the $AUC_{0-t}$ and $AUC_{0-\infty}$, test values were $110027.1{\pm}27786.4\;ng/mL{\cdpt}h$, $128807.0{\pm}34563.2\;ng/mL{\cdot}h$ and $105473.6{\pm}26496.2\;ng/mL{\cdot}h$, $125448.5{\pm}35975.5\;ng/mL{\cdot}h$, respectively. The 90% C.I. of $AUC_{0-t}$ were 0.97 to 1.10 and of $AUC_{0-\infty}$, 0.99 to 1.09 and thus were within the log 0.8-log 1.25 interval proposed by the KFDA. A two-way ANOVA showed no significant difference between the two formulations. Based on these statistical analysis, it was concluded that the test formulation is bioequivalent to the reference.

• Environmental Analysis Health and Toxicology
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• v.29
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• pp.4.1-4.10
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• 2014

Objectives Effects of nanoparticles including zinc oxide nanoparticles, titanium oxide nanoparticles, and their mixtures on skin corrosion and irritation were investigated by using in vitro 3D human skin models ($KeraSkin^{TM}$) and the results were compared to those of an in vivo animal test. Methods Skin models were incubated with nanoparticles for a definite time period and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide method. Skin corrosion and irritation were identified by the decreased viability based on the pre-determined threshold. Results Cell viability after exposure to nanomaterial was not decreased to the pre-determined threshold level, which was 15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure in the irritation test. IL-$1{\alpha}$ release and histopathological findings support the results of cell viability test. In vivo test using rabbits also showed non-corrosive and non-irritant results. Conclusions The findings provide the evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their mixture are 'non corrosive' and 'non-irritant' to the human skin by a globally harmonized classification system. In vivo test using animals can be replaced by an alternative in vitro test.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.239-244
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• 2003

This study investigated the in vivo insulin function of Polygonatum odoratum in normal and diabetic male Sprague-Dawley rats. Diabetes mellitus was induced by an i.p. injection of streptozotocin. Normal and diabetic rats were assigned to the diet groups of the control basal diet and Polygonatum odoratum diet. The animals were fed the diet and water ad libitum for 15 days. Initial and final body weights, total food intake and serum glucose and insulin levels were measured. An insulin suppression test was performed to elucidate the insulin function in the peripheral tissues. The results showed that the final serum glucose levels significantly decreased in the diabetic rats on the Polygonatum odoratum diet compared with the diabetic rats on the control diet. The final serum insulin levels were increased in the diabetic rats on the Polygonatum odoratum diet compared with the diabetic rats on the control diet. The in vivo function of the insulin increased in the diabetic rats on the Polygonatum odoratum compared with the diabetic rats on the control diet. These data indicate that Polygonatum odoratum may be beneficial in improving the in vivo insulin function in streptozotocin-induced diabetic rats.

• Corrosion Science and Technology
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• v.15 no.2
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• pp.43-53
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• 2016

In this study, electrochemical impedance spectroscopy (EIS) was used to examine the changes in the electrochemical properties of biodegradable pure magnesium implanted into Sprague-Dawley rats for three days. The in vivo test results were compared with those of the in vitro tests carried out in Hank's, dilute saline and simulated body fluid (SBF) solutions. The in vitro corrosion rates were 20~1700 fold higher, as compared to the in vivo corrosion rates. This discrepancy is caused by biomolecule adsorption on the surface, which prevents the transport of water into the magnesium surface on in vivo testing. Among the in vitro experimental conditions, the corrosion rate in SBF solution had the least difference from the in vivo implanted specimen.

• Fisheries and Aquatic Sciences
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• v.15 no.1
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• pp.73-76
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• 2012

Dichloromethane, ethanol, and boiling water extracts of the brown alga Ecklonia cava were examined in vivo for their antipyretic, analgesic, and anti-inflammatory activities in mice. These activities were evaluated by yeast-induced pyrexia, tail-flick test, and phorbol myristate acetate-induced inflammation (edema, erythema, and blood flow). Ethanol extract of E. cava (0.4 mg/ear) inhibited the inflammatory symptoms of mouse ear edema, erythema, and blood flow by 82.6%, 69.0%, and 65.4%, respectively. This extract also demonstrated potent analgesic activity. No acute toxicity was observed after p.o. administration of each extract (5 g/kg bw). These in vivo data are in agreement with the claims of the health care industry and indigenous medicine that E. cava is an effective remedy for inflammation-related symptoms.

• The Korean Journal of Pesticide Science
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• v.15 no.4
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• pp.374-382
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• 2011

We investigated the mutagenicity of methiozolin, newly developed herbicide, in vitro reverse mutation test using Salmonella typhimurium and Escherichia coli, chromosome aberration test using chinese hamster lung (CHL) cells and in vivo micronucleus test of mice. In the reverse mutation test, the methiozolin did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, Escherichia coli WP2uvrA with and without metabolic activation at $5,000{\mu}g$/plate. In the chromosome aberration test, the results showed no incidence of increased structural and numerical chromosome abberrations at any doses tested (80, 40, $20{\mu}g$/mL). In micronucleous test, the ratio of micronuclei was measured in polychromatic erythrocytes with treated methiozolin for ICR mice. No incidence of increased micronuclei were observed in polychromatic erythrocytes (1,500, 1,000, 500 mg/kg). Based on these results, we concluded that methiozolin has no mutagenic toxicity in vitro and in vivo systems.

• Toxicological Research
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• v.16 no.2
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• pp.109-116
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• 2000

The purposes of our study were to optimize the conditions of the screening and testing methods for endocrine disruptors, to characterize these assays using several compounds with well-defined endocrine activity, and to compare the sensitivity between these assays currently undergoing validation. Two in vitro test systems, MCF-7 cells proliferation (E-screen assay) and competitive binding to estrogen receptors (ER) were selected to evaluate the estrogenic effects. 17$\beta$-Estradiol (E2) and diethylstilbestrol (DES) were used as a positive control in vitro test. Also, E2 and ethinyl estradiol (EE) were used as a positive control in vivo uterotrophic assay. In in vitro test, E2 and DES showed a strong estrogenic response at concentration of 1.0 nM. In uterotrophic assay, E2 (0.3 $\mu\textrm{g}$/kg) and EE (0.3 $\mu\textrm{g}$/kg) produced a significant increase in uterus and vagina weight in both immature and ovariectomized rats. Although we did not com-pared the specificity between in vivo and in vitro assays, these assay systems may serve as a good tool for endocrine disruptors screening methods. Our data indicate that these assay systems exhibit some difference in their sensitivity to the same estrogenic compounds. Therefore, as a first rapid screening assay for estrogenic activity qf unknown chemicals, at least two assay systems should probably be carried out with a view of high sensitivity and standardization conditions. Also, a careful validation tests are necessary to obtain a reasonable degree of reproducibility.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.275-282
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• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

• YAKHAK HOEJI
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• v.39 no.4
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• pp.417-426
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• 1995

6-[(N-4-Chlorophenyl)amino]-7-chloro-5,8-quinolinedione (RCK20) was tested for antifungal activities, in vivo, against Candida albicans. RCK20 was compared vath ketoconazole and fluconazole in the treatment of systemic infection with Candida albicans in normal rats. The therapeutic potential of RCK20 had been assessed by evaluating their activities (survival rate) against systemic infections with in normal mice with Candida albicans. RCK20 improved survival rates as well as ketokonazole. RCK20 had ED$_{50}$. 0.25$\pm$0.18 mg/kg but ketoeonazole and fluconazole had ED$_{50}$, 8.00$\pm$0.73, 10$\pm$0.43 mg/kg respectively. Activities of RCK20 showed superior to that of ketoconazole and fluconazole. Intraperitoneauy administered RCK20 at the ED$_{50}$, 0.25 mg/kg for 7days and 14days reduced Candida albicans colony count in the kidneys and livers as well as ketoconazole and fluconazole at these ED$_{50}$, 8.00 and 10 mg/kg. Acute oral toxicity studies of RCK20 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK20 were low and LD$_{50}$ values were over 2.850 mg/kg in ICR mice. The Genotoxicities of RCK20 had been evaluated. RCK20 was negative in Ames test with Salmonella typhimurium (TA98 and TA100). The clastogenicity was tested on the RCK20 with in vivo mouse micronucleus assay. RCK20 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK20 has no genotoxic potential under these experimental condition.

• Food Science and Preservation
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• v.16 no.5
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• pp.782-788
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• 2009

The genotoxicological safety of gamma-irradiated egg white and yolk was examined to ensure that required safety parameters were met, and in an effort to further apply gamma-irradiation for improvement of the hygienic qualities of eggs. Egg white and yolk were irradiated at 20 kGy, much higher than the legally approved dose (less than 5 kGy), and possible genotoxicity was evaluated using in vitro and in vivo tests. The SOS chromotest employing Escherichia coli PQ37, and a chromosomal aberration test in cultured Chinese hamster lung (CHL) cells, were performed in vitro with or without metabolic activation (S9). An in vivo micronucleus development test was conducted using mouse bone marrow cells. Negative results were obtained in the SOS chromotest. The incidence of chromosomal aberration in CHL cells and the frequency of micronuclear developmentin mouse bone marrow cells treated with irradiated samples were not significantly different from those of non-irradiated controls. Thus, it may be concluded that up to 20 kGy of gamma irradiation applied to egg white and yolk did not show any genotoxic effects under our experimental conditions.