• Journal of Veterinary Science
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• v.21 no.5
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• pp.60.1-60.11
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• 2020

Background: Tumor-associated neoangiogenesis is a crucial target for antitumor therapies. Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies in dogs. Objectives: The aim of the study was to assess the pharmacokinetics of TAL after single oral administration in dogs. Additionally, the influence of feeding on the pharmacokinetic profile of TAL in dogs has been preliminarily investigated. Methods: Six healthy adult female Labradors were enrolled according to a randomized single-dose, 2-treatment, 2-phase, paired 2 × 2 cross-over study design. The dogs were administered a single 400 mg capsule of TAL in fasted and fed conditions. Blood was collected from 15 min to 48 h after dosing, and TAL quantified in plasma by a validated high-performance liquid chromatography method. The pharmacokinetics of TAL were analyzed using a non-compartmental approach. Results: TAL concentration was quantifiable up to 10 h and 24 h after fasted and fed conditions, respectively. C_max (fasted, 1.34 ± 0.12 ㎍/mL; fed, 2.47 ± 0.19 ㎍/mL) and T_max (fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t_1/2λz were significantly higher in fed (42.46 ± 6.64 mg × h/L; 17.14 ± 4.68 h) compared to fasted (12.38 ± 1.13 mg × h/L; 6.55 ± 1.25 h) dogs. The relative oral bioavailability of TAL for the fasted group was low (36.92% ± 3.28%). Conclusions: Feeding affects the pharmacokinetics of oral TAL in dogs, showing a delayed, but higher absorption with different rate of elimination. These findings are of importance in clinical veterinary settings, and represent a starting point for further related studies.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.291-297
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• 2001

The bioequivalence of two triflusal products was evaluated with 20 healthy volunteers following single oral dose according to the guidelines of Korea Food and Drug Administration (KFDA). Trisa $l^{R}$ capsule (Whanin Pharm. Corp., Korea) and Disgre $n^{R}$ capsule (Myung-In Pharm. Corp., Korea) were used as test product and reference product, respectively. Both products contain 300 mg of trifusal. One capsule of test product or reference product was orally administered to the volunteers, respectively, by randomized two period crossover study (2$\times$2 Latin square method). Blood samples were taken at predetermined time intervals for 4 hours and the determination of trifusal was accomplished using semi-microbore HPLC equipped with automated column switching system. The analytical method with HPLC was validated according to the Bioanalytic Method Validation guideline by F7A prior to determining the plasma samples. The pharmacokinetic parameters (AU $C_{0-4h}$ $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for statistical analysis of parameters. As a result of the assay validation, the limit of quantification of trifusal in human plasma by current assay procedure was 50 ng/ml using 500 $\mu$l of plasma. The accuracy of the assay was from 97.76% to 116.51% while the intra-day and inter-day coefficient of variation of the same concentration range was less than 15%. Average drug concentration at the designated time intervals and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05). The difference of mean AU $C_{olongrightarrow4hr}$, $C_{max}$, and $T_{max}$ between the two products (2.92, 4.39, and -2.44%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $C_{olongrightarrow4hr}$ and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different from each other (p>0.05). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two products of triflusal were bioequivalent.quivalent.ent.ent.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.220-229
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• 2008

Purpose: The present study was aimed to examine the effect of acellular dermal matrix ($AlloDerm^{(R)}$) grafted to the experimental tissue defect on tissue regeneration. Materials and Methods: Male albino rabbits were used. Soft tissue defects were prepared in the external abdominal oblique muscle. The animals were then divided into 3 groups by the graft material used: no graft, autogenous dermis graft, and $AlloDerm^{(R)}$ graft. The healing sites were histologically examined at weeks 4 and 8 after the graft. In another series, critical sized defects with 8-mm diameter were prepared in the right and left iliac bones. The animals were then divided into 5 groups: no graft, grafted with autogenous iliac bone, $AlloDerm^{(R)}$ graft, $AlloDerm^{(R)}$ graft impregnated with rhBMP-2, and $AlloDerm^{(R)}$ graft with rhTGF-${\beta}1$. The healing sites of bone defect were investigated with radiologic densitometry and histological evaluation at weeks 4 and 8 after the graft. Results: In the soft tissue defect, normal healing was seen in the group of no graft. Inflammatory cells and foreign body reactions were observed in the group of autogenous dermis graft, and the migration of fibroblasts and the formation of vessels into the collagen fibers were observed in the group of $AlloDerm^{(R)}$ graft. In the bone defect, the site of bone defect was healed by fibrous tissues in the group of no graft. The marked radiopacity and good regeneration were seen in the group of autogenous bone graft. There remained the traces of $AlloDerm^{(R)}$ with no satisfactory results in the group of $AlloDerm^{(R)}$ graft. In the groups of the $AlloDerm^{(R)}$ graft with rhBMP-2 or rhTGF-${\beta}1$, there were numerous osteoblasts in the boundary of the adjacent bone which was closely approximated to the $AlloDerm^{(R)}$ with regeneration features. However, the fibrous capsule also remained as in the group of $AlloDerm^{(R)}$ graft, which separated the $AlloDerm^{(R)}$ and the adjacent bone. Conclusions: These results suggest that $AlloDerm^{(R)}$ can be useful to substitute the autogenous dermis in the soft tissue defect. However, it may not be useful as a bone graft material or a carrier, since the bone defect was not completely healed by the bony tissue, regardless of the presence of osteogenic factors like rhBMP-2 or rhTGF-${\beta}1$.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.466-474
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• 2013

Despite the reports on safety concerns regarding the relationship between aluminum salts and neurological and bone disease, many countries continue to use aluminum as phosphate binders among patients with renal failure. In search for a diet supplement that could reduce aluminum toxicity related to renal failure, we carried out this prospective animal study in which the fenugreek seeds were assessed for their effects on rats nephrotoxicity induced by aluminum chloride ($AlCl_3$). Oral $AlCl_3$ administration during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) led to plasma biochemical changes, an inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status (TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in addition to kidney atrophy and morphological alterations at the level of Bowman's capsule, the glomerulus and different sorts of tubules, reminiscent of some known kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in the diet) during the last 2 months showed its effectiveness in restoring normal plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the TAS, inhibiting LPO and alleviating histopathological changes in the injured kidneys. This study highlights the induced nephrotoxicicity, as well as the related toxicity in the brain and bone, by chronic oral ingestion of the aluminum salts. However, the maintenance of a diet supplemented with fenugreek seeds could offer protection for the kidney, bone and brain, at the same time.

• Journal of Pharmaceutical Investigation
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• v.32 no.1
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• pp.27-33
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• 2002

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor $EL^{\circledR},\;Labrasol^{circledR}$, and Lauroglycol $FCC^{circledR}$ was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher $C_{max}$ and greater $AUC_{0-5hr}$ than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

• Parasites, Hosts and Diseases
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• v.57 no.5
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• pp.521-524
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• 2019

We are going to describe the female soboliphymid nematodes, which were recovered from the stomach of a Asian badger, Meles leucurus (Mammalia: Mustelidae), in Geochang-gun, Gyeongsangnam-do, Korea. In February 1998, we found 2 peculiar nematodes with a cup-like organ in the anterior end from the stomach of badger. Recovered worms were fixed with 10% formalin, cleared in glycerin-alcohol solution and observed under a light microscope with a micrometer. They were 34.46 (33.43-35.50) mm long by 2.13 mm at maximum width. Cephalic sucker cup-like, 3.34 (3.13-3.55) mm wide, 2.40 (2.25-2.55) mm long, with the oral aperture and meridionally striated on the buccal capsule. Oral aperture 2.38 mm in diameter. Circumoral membrane 0.41 (0.38-0.45) mm wide. Esophagus muscular, 4.81 (4.50-5.00) mm long by 0.80 (0.78-0.83) mm at maximum width. Vulva situated at 3.13 mm ventro-anterior level from the esophago-intestinal junction. Vagina anteriad, 3.38 mm long, making a canal from the uterus to the vulva opening. Uterus single, large. Tail 0.35 (0.33-0.38) mm long. Intrauterine eggs long elliptical, 0.058-0.065 (0.062) mm long and 0.030-0.033 (0.031) mm wide. Based on the some morphological characters and host-specificity, our specimens are nearly identical with S. baturini. Therefore, the present report describes S. baturini for the first time in Korea.

• The Journal of Pediatrics of Korean Medicine
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• v.35 no.4
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• pp.141-155
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• 2021

Objective The purpose of this study is to gather information from clinical studies conducted in China and analyze the effects of herbal medicine treatment for childhood vitiligo. Methods The randomized controlled trials (RCTs) with herbal medicine treatment for childhood vitiligo from the Chinese Academic Journal (CAJ) from China National Knowledge Infrastructure (CNKI) were searched. Then, each study was analyzed by demographics, disease durations, interventions, treatment periods, outcomes, adverse events, and compositions of the herbal medicine used. Result A total of 6 RCTs were included. All the trials except for one used a combination of Chinese herbal medicine with Western medicine as their treatment groups. The total efficacy rate was used to measure the effectiveness, and the treatment groups reported a significantly higher total efficacy rate compared to the control groups in all studies. In one study, a control group treated with compound glycyrrhizin capsule and topical compound kaliziran tincture combination treatment was compared with a treatment group which used the same treatment that the control group received in addition to oral herbal medicine. This study also showed higher total effectiveness in the treatment group than the control group. Conclusions In pediatric vitiligo, a combination of herbal medicine treatment rather than Western medical treatment alone can improve symptoms. In addition, it was suggested that the therapeutic effect can be enhanced when oral herbal medicine is used in combination with other herbal medicine treatments.

• Toxicological Research
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• v.21 no.1
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• pp.51-55
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• 2005

To investigate the acute toxicity of adventitious roots extract derived from wild ginseng, it was orally administered to beagle dogs with a single dose. In acute toxicity test, three groups (9 beagle dogs of male) were administered with different dosages of adventitious roots extract (prepared by Biopia Corp.) 500 mg/kg (G2), 1,000 mg/kg (G3), 2,000 mg/kg (G4) and one group (G1, 2 beagle dogs of male) were received by only capsule without the extract according to the Regulation on Korea Food and Drug Administration (1999. 12. 22). There were vomitus for a time and mucous stool at the day, and anorexia and mucous stool at the first day in the group of 2,000 mg/kg administration. There were mucous stool in one and anorexia for a while in two beagle dogs at the first day in the 1,000 mg/kg administration. But no death or abnormal clinical sign was observed through the study period. Therefore, the adventitious roots extract derived from wild ginseng is considered not to have the acute toxicity in the beagle dogs. These results suggest that LD/sub 50/ value of the test substance was considered to be more than 2,000 mg/kg in the beagle dogs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.282-282
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• 1996

The purpose of this study was to prepare the nifedipine dry elixir (NDE) and coated nifedipine dry elixir (CNDE) containing nifedipine ethanol solution for improving the dissolution rate and bioavailability of nifedipine. NDE containing nifedipine and ethanol in wall materials of dextrin was prepared using a spray-dryer and then NDE was coated with eudragit acrylic resin to make CNDE. Shape and size of the NDE and CNDE were monitored by scanning electron micrograph and laser particle size analyzer In vitro dissolution tests were performed in simulated gastric and intestinal fluid. Bioavailability of NDE and CNDE were compared with drug powder suspension and commercial soft capsule after oral administration of the preparations to rats. NDE and CNDE are spherical in shape. Cross-sectional view of dry elixirs indicates the large inter cavity containing ethanolic drug solution in shell. Geometric mean diameter of NDE and CNDE is about 6.64 and 8.70 $\mu\textrm{m}$, respectively. Drug dissolution rate within first 5 min from NDE increased dramatically irrespective of dissolution medium. However, CNDE showed a particularly retarded dissolution rate in pH 1.2 simulated gastric fluid compared with NDE. The bioavailability of nifedipine in the NDE was increased dramatically compared with drug powder suspension. CNDE reduced initial burst-out plasma peak compared with NDE. CNDE as a sustained release delivery system could reduce the initial burst-out plasma peak due to controlling the release rate of nifedipine from NDE and maintain the effective plasma level over a longer period within therapeutic window with enhanced bioavailability of nifedipine.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.1-9
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• 1994

In order to assay the human plasma concentration of nifedipine in patients with bronchopulmonary dysplasia (BPD) and pulmonary hypertension, a modified high performance liquid chromatography (HPLC) method was applied. The retention times for nifedipine and an internal standard (11-ketoprogesterone) were $10.5\;{\pm}\;0.41$ and $13.1\;{\pm}\;0.63$ min, respectively. Absolute recovery from the plasma was $102.9\;{\pm}\;7.07%$. Reproducibility was excellent and variability between the runs was small. There was a negligible degradation during the assay procedure. The calibration curve shows a good linearity in the range of the desired plasma concentrations of nifedipine. A stability test of nifedipine in the human plasma shows 8 and 13% degradation during the storage of 5 and 9 months, respectively. There were no interferences on the HPLC assay with any possible medications for the BPD. The method has been used to monitor the drug concentrations in a patient. The concentration-time curve of a patient after a single oral dose of 0.3 mg/kg shows a double-peak phenomenon that was quite different from the previous report, suggesting non-bolus administration. However the hemodynamic responses were corresponding to the plasma concentration levels of nifedipine.