• Journal of Ginseng Research
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• 제44권2호
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• pp.229-237
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• 2020

Background: We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings. Methods: Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods. Results: Repeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract. Conclusion: A good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K.

• 동의생리병리학회지
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• 제22권2호
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• pp.296-301
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• 2008

The purpose of this study was to examine to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated to ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg/p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

• Journal of Ginseng Research
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• 제23권2호
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• pp.115-121
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• 1999

에탄올 단기 투여로 유발되는 기억획득의 손상에 대한 홍삼 조 사포닌 성분을 비롯한 수종의 뇌기능개선 후보약물의 급성 및 연속 투여 작용을 검토하였다. 에탄올 급성 투여로 유발된 학습획득 손상 흰쥐에 GABA신경 억제 성 약물인 picrotoxin 급성 투여시 에탄올 투여 흰쥐의 학습획득 손상 작용은 유의성 있는 개선효과를 나타내었으나 diazepam, acetyl-L-carnitine 및 apomoiphie투여 군은 현저한 영향을 미치지 않았다. 급성 홍삼 total saponin 투여군은 에탄올 투여 흰쥐의 학습획득 손상을 유의성 있게 억제하였으며 7일간의 연속 투여에 의해 그 효과가 현저하게 증가하였다. 급성 및 연속 deprenyl투여군은 모두 유의성 있는 억제 작용을 나타내었으나 protopanaxatriol, protopanaxadiol 및 centrophenoxine 투여 군은 모두 현저한 억제작용을 나타내지 않았다. 급성 piracetam 투여 및 연속 N-methyl-D-glucamine투여 군은 유의성 있는 억제효과를 나타내었다. 한편, 에탄올 투여 희쥐의 학습획득 손상에 대한 홍삼 total saponin 연속 투여효과는 ${\alpha}-methyl-전 처치에 의해 유의성 있게 차단되었으나 N-methyl-D-glucamine 연속투여에 의한 억제효과는 부분적으로 차단되었으며, 연속 depreny의 효과는 용량에 따라 차단 또는 증강되는 등 전혀 다른 효과를 나타내었다. 이러한 결과는 에탄올 급성 투여 흰쥐의 학습획득 손상은 picrotoxine, 홍삼 조사포닌, N-methyl-D-glucamme및 deprenyl의 급성 또는 연속 투여가 효과적이며 홍삼 조 사포닌과 N-methyl-D-glucamine 및 deprenyl의 연속 투여 효과는 뇌중 도파민 신경활성에 미치는 영향이 상위함을 나타내고 있다. 따라서 에탄올 급성투여 흰쥐의 학습획득 손상은 일차적으로 뇌중 GABA 신경활성의 억제에 기인하며 이차적으로 도파민신경활성과의 균형의 중요성을 시사하고 있다.

• 약학회지
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• 제40권5호
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• pp.491-500
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• 1996

The organ distribution and pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), were compared after single and repeated subcutaneous administration ( 50${\mu}$/kg, 10${\mu}g$Ci/kg of $^{125}I$-DWP401, twice a day for 7 consecutive days) to rats. The pharmacokinetic parameters such as AUC and terminal half-life were similar between two different administration. During repeated administration, the plasma concentration of DWP401 seemed to be constant when the plasma was collected at 15 min after each dosing. The TCA-precipitated radioactivities in thyroid, liver, kidney, and stomach were higher than those of other organs studied after both single and repeated administration. The TCA-precipitated radioactivities after repeated administration in several organs, such as thyroid, stomach, prostate, adrenal, eye ball, and testis were higher than those after single administration. But, according to the observations using gel filtration chromatography and antibody binding assay, the radioactivities in thyroid and stomach were not primarily due to the intact DWP401 or its metabolites but due to the $^{125}I$-thyroxine binding protein. In conclusion, it can be suggested that DWP401 is metabolized to each amino acid or small polypeptides, and there was no significant changes in pharmacokinetics or any indications for accumulation of DWP401 in rat plasma and organs after repeated treatment.

• Journal of Yeungnam Medical Science
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• 제4권1호
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• pp.89-96
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• 1987

동물의 간소엽에 심한 지방성병변과 괴사성병변을 일으키는 사염화탄소와 이와 비슷한 독작용을 가지고 동물의 간소엽에 심한 출혈성 괴사성병변을 초래하는 Dimethylnitrosamine이 동일물질의 2~3회 반복투여에 의해서 어떠한 영향을 받는가를 비교, 관찰하기 위하여 체중 150~200gm의 백서를 실험동물로 사용하여 Sublethal dose의 사염화탄소(0.4ml/kg)와 DMN(40mg/kg)을 1회, 2회 및 3회 복강내로 주입하여 간소엽에 나타난 병리조직학적 병변을 요약하면 다음과 같다. 1. 사염화탄소를 1회 투여한 동물의 간소엽에 있어서 지방변성 괴사성병변에 비해 2회 또는 3회 반복투여한 동물의 병변정도가 경하였고, 또 간세포나 동양세포의 재생성 변화도 더 빨리 일어났다. 2. DMN을 1회 투여한 동물에 있어서의 괴사성병변은 2회 또는 3회 투여한 군의 그것과 큰 차이는 없었지만 간세포의 증식성 변화는 DMN의 투여회수가 많을수록 비례해서 강하게 나타나는 경향을 보였다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• Asian-Australasian Journal of Animal Sciences
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• 제25권6호
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• pp.785-788
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• 2012

The aim of the present study was to clarify the effect of kisspeptin-10 on LH secretion in prepubertal ewes. In experiment 1, prepubertal ewes fitted with indwelling jugular catheters were randomly assigned to receive 0, 0.5, 1 or 2 mg of kisspeptin-10 dissolved in saline, and serial blood samples were collected at 15-min intervals for 180 min to analyze the response curves of LH after injection. In experiment 2, prepubertal ewes fitted with indwelling jugular catheters were injected with 0 or 1 mg of kisspeptin-10 dissolved in saline and the injection was repeated 3 times at 1 h interval and serial blood samples were collected at 15-min intervals for 210 min to analyze the response curves of LH after injection. The results showed that single intravenous administration of 0.5, 1 and 2 mg of kisspeptin-10 all could significantly increased LH secretion in prepubertal ewes, and the effect of 1 and 2 mg of kisspeptin-10 on LH secretion was higher than that of 0.5 mg group. The results also showed that repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion and repeated administration did not influence the effect of kisspeptin-10 on LH secretion in prepubertal ewe. In conclusion, the present study indicated that single or repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion in prepubertal ewes.

• 대한예방한의학회지
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• 제20권2호
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• pp.97-109
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• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• 대한예방한의학회지
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• 제19권1호
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• pp.145-159
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• 2015

Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

• 대한의생명과학회지
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• 제25권3호
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• pp.247-255
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• 2019

Curcuma longa L. (C.L), Curcuma aromatica Salisb. (C.A) and Zingiber officinale Rosc. (Z.O) of Zingiberaceae plants which are well known as effects of natural anti-oxidant, anti-cancer and anti-inflammatory. We examined that the Zingiberaceae plants are involved in development and modulation of orofacial pain in rats. Male, 7- to 8-week-old, Sprague-Dawley rats weighing 240~280 g were used in this study. Experiments were performed using acute pain model that was caused by the injection of 5% formalin into the right vibrissa pad. The number of scratching or rubbing to the injection site was recorded for 9 consecutive 5-minute intervals following injection of formalin. The experimental groups were acute orofacial inflammatory pain; control group (formalin, 5%), vehicle group (5% formalin after sodium carboxymethyl cellulose), single administration group, single mixed administration group, repeated administration group. The experiments were performed various concentrations of Zingiberaceae plants extract. Therefore, oral administration of C.L, C.A, and Z.O (p.o., concentrations of 12.5, 25 mg/mL) in orofacial inflammatory pain model substantially decrease the nociceptive behavior in a concentration dependent manner. And it tended to decrease at low concentration (12.5 mg/mL) of single mixed and repeated administration more than single administration. This result means that Zingiberaceae plants extract affects the modulation of acute orofacial inflammatory pain. Thus, Zingiberaceae plants extract may be a potential therapeutic treatment for orofacial inflammatory pain.