• Title/Summary/Keyword: Cmax

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Comparative Studies on Concentration of Decursinol in Plasma after Oral Administration of Angelicae Gigantis Radix Extract and Combined Use of Decursin and Cnidii Rhizoma Extract or Bupleuri Radix Extract in Rats (당귀와 천궁 및 시호의 병용 경구 투여에서 흰쥐 혈중 Decursinol 농도의 비교 검토)

  • Park, Roh-Jeong;Kim, Nam-Jae;Lee, Kyung-Tae;Seo, Seong-Hoon
    • Korean Journal of Pharmacognosy
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    • v.32 no.1 s.124
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    • pp.72-78
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    • 2001
  • This study was performed to elucidate the influence on the plasma decursinol concentration after administration of combined decursin and Cnidii Rhizoma or decurisin and Bupleuri Radix extracts in comparison with single decursin administration. The identification of decursinol isolated from Angelica gigas was carried out by GC/MS and the concentration of decursinol in the plasma after oral administration was determined by HPLC. The value of area under the plasma concentration (AUC) and the maximal concentration (Cmax) of decursinol after administration of methanol and ether Angelicae Gigantis Radix extract was higher than those of single decursin-treated group. It was also found that the AUC and the Cmax of decursinol after combined administration with decursin and Cnidii Rhizoma were higher than those of decursin administration, whereas those of combined with decursin and Bupleuri Radix was lower. Moreover, the studies were performed with decursinol only or with combined decursinol and Cnidii Rhizoma/Bupleuri Radix, both of combined treatment increased the plasma decursinol concentrations compared with decursinol-treated group in rats. On the basis of these results, it is concluded that co-existing substances or co-administration with other drugs may influence the plasma levels of decurisinol after oral administration.

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Studies on Pharmacokinetics of a new NSAID SJ-151(I)

  • Kim, Dong-Sup;Chung, Hye-Joo;Na, Han-Kwang;Park, Yoon-Ju;In Sook, Park;Ahn, Mi-Lyung;Chang, Young-Sup
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.220-220
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    • 1996
  • The objectives of this study were to evaluate the pharmacokinetics of SJ-151 which is a new NSAID in male Beagle dogs following a single oral dosing. Seven beagle dogs (10-l2kg) were all administered a single oral gavage(10mg/kg) of SJ-151 tablet and serial blood samples of approximately 5$m\ell$ were then drawn from the cephalic vein of each animal at 0(predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24hours postdosc. SJ-151 (Cinmetacinㆍbutendiol)and cimetacin were quantified in the plasma fraction by HPLC assay. The pharmacokinetic parameters calculated from the plasma concentrations of SJ-151 in dayl are Cmax(ng/$m\ell$)509$\pm$248, Tmax(hr) 1.50$\pm$0.45, AUC(ng.hr/$m\ell$) 1,750$\pm$762, tl/2$\alpha$ 0.98$\pm$0.30, t1/2$\beta$ 12.0$\pm$6.75. The pharmacokinetic parameters calculated from the plasma concentrations of Cinmetacin in day 1 are Cmax(ng/$m\ell$)258$\pm$74.1, Tmax(hr)2.42$\pm$ 0.92, AUC(ng.hr/$m\ell$) 1,820$\pm$318, t1/2$\alpha$ 1.74$\pm$0.49, t1/2$\beta$ 25.4$\pm$13.4.

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Effects of mixed formulation of tamoxifen and blue honeysuckle on the pharmacokinetics profiles of tamoxifen after single oral administration

  • Hu, Jin-Ryul;Jang, Tae-Woo;Kang, Su-Jin;Ku, Sae-Kwang;Choi, Seong-Hun;Lee, Young-Joon
    • The Journal of Korean Medicine
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    • v.40 no.4
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    • pp.1-15
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    • 2019
  • Objectives: Here, we investigated the effects of concentrated and lyophilized powders Blue honeysuckle (BH) on the PK of tamoxifen, to establish the pharmacokinetics (PK) profiles as one of essential process in new drug development. Methods: After single oral treatment of 0.4 mg/ml of tamoxifen or tamoxifen 0.4 with BH 40, 20 and 10 mg/ml, the plasma were collected at 0.5 hr before administration, 0.5, 1, 2, 3, 4, 6, 8 and 24 hr after end of single or mixed formula treatment. Plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf were analyzed using noncompartmental PK data analyzer programs. Results: Tamoxifen and BH 40 mg/ml did not induce any significant change on the plasma tamoxifen concentrations, while significant decreases were observed in tamoxifen and BH 10 mg/ml from 2 to 8 hr as compared with tamoxifen only, respectively. Furthermore, significant increases of Tmax in tamoxifen and BH 40 mg/ml, significant decreases of Cmax in tamoxifen and BH 20 mg/ml, significant decreases of AUC0-t, AUC0-inf and MRTinf in tamoxifen and BH 10 mg/ml were demonstrated as compared with tamoxifen only. Conclusion: Taken together, tamoxifen and BH 10 mg/ml induced significant decrease of the oral bioavailability of tamoxifen, while tamoxifen and BH 40 or 20 mg/ml did not critically influenced, suggesting formulated BH concentration-independencies. It, therefore, seems to be needed that pharmacokinetic study after repeated administration should be tested to conclude the effects of BH on the pharmacokinetics of tamoxifen.

Toxicity Screening After Single Dose of a Newly Developed Oral Heparin Derivative in Male Cynomolgus Monkeys (게잡이 원숭이에 있어 새로운 헤파린유도체의 단회투여 독성스크리닝)

  • Kim, Choong-Yong;Kim, Sang-Kyoon;Woo, Young-Ah;Jeong, Eun-Ju;Han, Su-Cheol;Heo, Jeong-Doo;Park, Kui-Lea;Byun, Young-Ro
    • Toxicological Research
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    • v.23 no.2
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    • pp.159-164
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    • 2007
  • Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.

A study of the microstructures and electrical properties of $ZrO_2$ thin film on Si(100) (증착조건 및 열처리조건에 따른 $ZrO_2$박막의 미세구조와 전기적 특성에 관한 연구)

  • 유정호;남석우;고대홍;오상호;박찬경
    • Journal of the Korean Vacuum Society
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    • v.9 no.4
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    • pp.341-345
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    • 2000
  • We investigated the microstructures and the electrical properties of $ZrO_2$thin films deposited by reactive DC magnetron sputtering on (100) Si with different deposition conditions and annealing treatments. The refractive index of the $ZrO_2$ thin films increased with annealing temperatures and deposition powers, and approached to the ideal value of 2.0~2.2. The $ZrO_2$thin films deposited at the room temperature are amorphous, and the films are polycrystalline at the deposition temperature of $300^{\circ}C$. Both the thickness of the interfacial oxide layer and the root-mean-square (RMS) value of surface roughness increased upon annealing in the oxygen ambient. The Cmax value and leakage current value decreased with the increase of thickness of the interfacial oxide thickness.

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Bioequivalence of Dybis Tablet (Metformin Hydrochloride 500 mg) (다이비스 정 (염산메트폴민 500 mg)의 생물학적 동등성)

  • 최준식;박영진;박상묵;범진필
    • YAKHAK HOEJI
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    • v.47 no.4
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    • pp.239-243
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    • 2003
  • Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. The purpose of the present study was to evaluate the bioequivalence of two metformin hydrochloride tablets, Glucophage tablet (DaeWoong Pharmaceutical Co., reference drug) and Dybis tablet (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four normal volunteers, 26.6$\pm$4.01 years in age and 60.6$\pm$9.80 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of metformin hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin hydrochloride in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt, Cmax and Tmax between two products were -1.05%, -6.76% and -4.51%, respectively, when calculated against the reference drug. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8$\leq$$\delta$$\leq$log1.25 (e.g., log0.9082$\leq$$\delta$$\leq$log1.0906 and log0.8188$\leq$$\delta$$\leq$log1.0392 for $AUC_{t}$ and $C_{max}$, respectively). The 90% confidence intervals using untransformed data was within $\pm$20% (e.g., -17.66%$\leq$$\delta$$\leq$8.63% for $T_{max}$). All parameters met the criteria of KFDA for bioequivalence, indicating that Dybis tablets (Shinpoong Pharmaceutical Co.) is bioequivalent to Glucophage tablets (DaeWoong Pharmaceutical Co.).

Bio-Equivalence Analysis using Linear Mixed Model (선형혼합모형을 활용한 생물학적 동등성 분석)

  • An, Hyungmi;Lee, Youngjo;Yu, Kyung-Sang
    • The Korean Journal of Applied Statistics
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    • v.28 no.2
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    • pp.289-294
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    • 2015
  • Linear mixed models are commonly used in the clinical pharmaceutical studies to analyze repeated measures such as the crossover study data of bioequivalence studies. In these models, random effects describe the correlation between repeated outcomes and variance-covariance matrix explain within-subject variabilities. Bioequivalence analysis verifies whether a 90% confidence interval for geometric mean ratio of Cmax and AUC between reference drug and test drug is included in the bioequivalence margin [0.8, 1.25] performed using linear mixed models with period, sequence and treatment effects as fixed and sequence nested subject effects as random. A Levofloxacin study is referred to for an example of real data analysis.

Pharmacokinetics of Oral Administration of Oxytetracycline in Eel, Anguilla japonica (Oxytetracycline의 경구 투여에 따른 뱀장어 체내 약물동태학적 특성)

  • Kim, Jin-Do;Seo, Jung-Soo;Kim, Ju-Wan;Lee, Joo-Seok;Jung, Sung-Hee;Ji, Bo-Young;Kim, Jin-Woo;Kim, Eung-Oh
    • Journal of fish pathology
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    • v.21 no.2
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    • pp.119-127
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    • 2008
  • Oxytetracycline (OTC) has been widely used in eel culture as a therapeutic and prophylactic agent because of its broad-spectrum activity against gram-positive and -negative bacteria. The oral treatment dosage of OTC approved for the treatment of edwardsiellosis, furunculosis and vibriosis in eel is 50 mg/kg/day for 3-7 days in Korea. To determine new optimum dose of OTC in eel, the pharmacokinetics of OTC after single oral administration (100 mg/kg B.W., 200 mg/kg B.W.) in cultured eel, Anguilla japonica was examined. In oral dosage of 100 and 200 mg/kg body weight, the highest plasma concentrations of OTC were 1.19±0.42 ㎍/㎖ and 2.69±0.57 ㎍/㎖, respectively. Plasma concentrations of OTC were not detected after 720 h post-dose in all experiments. The kinetic profile of absorption, distribution and elimination of OTC in plasma wwas calculated fitting to a 1- and 2-compartment model by WinNonlin program. The following parameters were obtained for a single dosage of 100 and 200 mg/kg respectively: 1-compartment model, AUC= 82.48 and 432.68 ㎍*h/㎖, Tmax= 3.93 and 14.24 hr, Cmax= 0.94 and 2.34 ㎕/㎖; 2-compartment model, AUC= 448.73 and 530.65 ㎍*h/㎖, Tmax= 6.37 and 8.96 hr, Cmax= 0.90 and 3.21 ㎕/㎖.

Pharmacokinetics of oxytetracycline in olive flounder (Paralichthys olivaceus) by dipping and oral administration (Oxytetracycline의 약욕 및 경구투여에 따른 넙치(Paralichthys olivaceus) 체내 약물동태학적 특성)

  • Jung, Sung-Hee;Choi, Dong-Lim;Kim, Jin-Woo;Jo, Mi-Ra;Seo, Jung-Soo;Jee, Bo-Young
    • Journal of fish pathology
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    • v.21 no.2
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    • pp.107-117
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    • 2008
  • The pharmacokinetic properties of oxytetracycline (OTC) were studied after dipping and oral administration to cultured olive flounder, Paralichthys olivaceus (600 g). Plasma concentrations of OTC were determined after oral dosage (50, 100 and 200 mg/kg body weight) and dipping (50, 100 and 200 ppm, 1 h) in olive flounder (average 600 g, 23±1℃). Plasma samples were taken at 3, 5, 10, 15, 24, 32, 48, 72, 120, 168 and 240 h post-dose. In oral dosage of 50, 100 and 200 mg/kg, the peak plasma concentrations of OTC, which attained at 3 h post-dose, were 0.34, 0.44 and 1.18 ㎍/㎖, respectively. In dipping of 50, 100 and 200 ppm, those of OTC which also observed at 5 h post-dose, were 0.43, 0.38 and 0.64 ㎍/㎖, respectively. Plasma concentrations of OTC were not measurable at 240 h post-dose in all experiments. The kinetic profile of absorption, distribution and elimination of OTC in plasma were analyzed fitting to a one-compartment model by WinNonlin program. The following parameters were calculated for a single dosage of 50, 100 and 200 mg/kg body weight, respectively: AUC (the area under the concentration-time curve)=31.40, 28.07 and 32.97 ㎍∙h/㎖; T1/2 (half-life)􀆫0.89, 1.12 and 0.43 h; Tmax (time for maximum concentration)= 5.25, 3.70 and 7.30 h, Cmax (maximum concentration)=0.25, 0.38 and 0.61 ㎕/㎖. Following dipping at 50, 100 and 200 ppm, these parameters were AUC􀆫15.51, 14.63 and 19.72 ㎍∙h/㎖; T1/2= 0.75, 0.41 and 0.74 h; Tmax=4.90, 7.08 and 4.68 h, Cmax=0.40, 0.32 and 0.46 ㎕/㎖.

Prediction of Stream Flow on Probability Distributed Model using Multi-objective Function (다목적함수를 이용한 PDM 모형의 유량 분석)

  • Ahn, Sang-Eok;Lee, Hyo-Sang;Jeon, Min-Woo
    • Journal of the Korean Society of Hazard Mitigation
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    • v.9 no.5
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    • pp.93-102
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    • 2009
  • A prediction of streamflow based on multi-objective function is presented to check the performance of Probability Distributed Model(PDM) in Miho stream basin, Chungcheongbuk-do, Korea. PDM is a lumped conceptual rainfall runoff model which has been widely used for flood prevention activities in UK Environmental Agency. The Monte Carlo Analysis Toolkit(MCAT) is a numerical analysis tools based on population sampling, which allows evaluation of performance, identifiability, regional sensitivity and etc. PDM is calibrated for five model parameters by using MCAT. The results show that the performance of model parameters(cmax and k(q)) indicates high identifiability and the others obtain equifinality. In addition, the multi-objective function is applied to PDM for seeking suitable model parameters. The solution of the multi-objective function consists of the Pareto solution accounting to various trade-offs between the different objective functions considering properties of hydrograph. The result indicated the performance of model and simulated hydrograph are acceptable in terms on Nash Sutcliffe Effciency*(=0.035), FSB(=0.161), and FDBH(=0.809) to calibration periods, validation periods as well.