• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.493-497
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• 2011

The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 9.1 ${\mu}M$. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration ($C_{max}$) was significantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was significantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.

• Journal of Oral Medicine and Pain
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• v.20 no.1
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• pp.67-77
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• 1995

A Case of pemphigus bulgaris in buccal mucosa of 48 years old Korean female was reported. Final diagnosis was determined by evaluation of clinical and histopathological finding. The patient could be treated successfully by administration of prednisolone, injection of bethametasone, application of oramedy and irradiation of soft laser.

• Journal of Oral Medicine and Pain
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• v.21 no.1
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• pp.79-87
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• 1996

The purpose of this study was to assess the vascular changes after thermophysical therapies using ice pack and ultrasound, investgate the mechanism of peripheral vasodilation by sympathetic nerve, and to observe the effects of the ergotamine to the thermophysical therapy. The author had used 16 healthy rabbits which were divided into 2 groups : with and without administration of ergotamine. Experimental animals were sacrificed 5, 10, 20 minutes after experiment, and were examined with gross and stereoscope of resin casting blood vessel models. The results were as follows : 1. Vasodilation was not remarkably found in the group with administration of egrotamine after thermophysical therapy. 2. Vasodilation was remarkably found in the group without administration of ergotamine after thermophysical therapy. 3. Vasodilation was increased in the group without administration of ergotamine, but not remarkably found in the group with administration of ergotamine in lapse of time 4. Thermophysical therapy was most effective to arterioles. Our data suggest that the dilation of peripheral blood vessels from thermophysical therapy was controlled by sympathetic nerve, because the blood vessels did not changed after administration of ergotamines which was a sympathetic nerve blocker.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.245.1-245.1
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• 2003

DA-8159 is a new PDEV (Phosphodiesterase V) inhibitor, synthesized by Dong-A Pharm., as an oral agent to treat male erectile dysfunction. To make a selection of the dosage of oral administration in carcinogenic studies, we studied preliminarily the pharmacokinetics of DA-8159 after single (at the 1$\^$st/ day) and 1-week (at the 7$\^$th/ day) oral administrations of the drug at doses of 15, 50 and 150 mg/kg/day, to male ICR mice. In 15mg/kg single and 1-week repeated oral administration groups, the concentrations of DA-8159 and DA-8164(the main metabolite of DA-8159) were below the limit of quantitation(LOQ:50ng/ml). (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1399-1403
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• 2009

The aim of the present study was to evaluate the possibility of protective effectness of swimming exercise and Gastrodia elata blume oral administration against beta-cell damage in streptozotocin (STZ)-induced diabetes in rats. The animals were divided into five groups: the normal group(n=10), the STZ-induced diabetes group(n=10), the STZ-induced diabetes and moderate-intensity exercise group(n=10), the STZ-induced diabetes Gastrodia elata blume(300 mg/kg) oral administration group(n=10), the STZ-induced diabetes and moderate-intensity exercise and Gastrodia elata blume(300 mg/kg) oral administration group(n=10). Animals in the exercise groups were made to swim moderate swimming exercise protocols once a day for 4 consecutive weeks. Serum glucose concentration and insulin level, superoxide dismutase (SOD) and catalase (CAT) were measured in serum. Swimming exercise and Gastrodia elata blume extract administration has shown anti-diabetic effect probably through decreasing serum glucose and insulin level and increasing antioxidant enzyme activity.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.16.1-16.9
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• 2016

Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.471-481
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• 2005

In Korea, generic drug and bioequivalence test are the hot issues since a new medical system of separation of dispensary from medical practice was started in 2000. The KFDA(Korea FDA) had revised several times ${\ulcorner}Guidance\;for\;bioequivalence\;test{\lrcorner}$. In vitro dissolution test has been extensively used as a quality control tool for solid oral dosage forms. In an effort to minimize unnecessary human testing, in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part on extended release drug product development. The recently published US guidance, ${\ulcorner}Extended\;release\;oral\;dosage\;forms\;:\;development,\;evaluation,\;and\;application\;of\;in\;vitro/in\;vivo\;correlations{\lrcorner}$ will be helpful for us to make our own guideline.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.17-23
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• 1997

A saline suspension of Lumbricus rubellus earthworm powder (EWP) was administered to rats (1 g/kg/day) orally for 15 days to evaluate an oral effectiveness for thrombotic disorders. Blood was drawn at 2-day interval after the administration. Several parameters for antithrombotic, anticoagulant and fibrinolytic activities were measured, including platelet aggregation, clotting time, plasmin activity and the levels of FDP (fibrin/fibrinogen degradation products), D-dimer, and t-PA antigen. It did not affect platelet aggregation induced by ADP and collagen but anticoagulant activity (aPTT and TT) was gradually increased to two-folds for the first 5 days of administration and back to normal. Fibrinolytic activity of euglobulin fraction was highest on the 11 th day after the administration. The level of FDP was elevated to be comparable to the positve control$ (5-10 {\mu}g/ml)$ after 9-day treatment. Oral administration of the EWP could also reduce the formation of venous thrombus induced with viper venom. Complete blood count (CBC) profiles were within normal ranges except for a slight increase in white blood cells after the oral administration for 15 days. These results suggested that the EWP may be valuable for the prevention and/or treatment of thrombotic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.4
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• pp.201-208
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• 2020

The effects of Gamisoyo-san (GMSYS) co-administration within 5 min on the pharmacokinetics (PK) of tamoxifen were observed. After 50 mg/kg of tamoxifen oral treatment, GMSYS 100 mg/kg was orally administered within 5 min to 7-wk old male SPF.VAF Outbred Crl:CD [Sprague-Dawley (SD)] rats. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf of tamoxifen were analysis as compared with tamoxifen single administered rats. Although co-administration with GMSYS did not critically influenced on the pharmacokinetic parameters of oral tamoxifen, they induced increased trends of plasma tamoxifen concentrations, especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 hr after end of co-administration with GMSYS as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMSYS 100 mg/kg within 5 min. It is considered that pharmacokinetic studies should be tested like the effects of GMSYS on the pharmacokinetics of tamoxifen, when they were co-administered with prolonger intervals than Tmax of tamoxifen oral administration (about 2.5 hr-intervals), to achieve the optimal dosing regimen of GMSYS and tamoxifen co-administration.