• Title/Summary/Keyword: $C_{max}$

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Pharmacokinetic Interaction between Nisoldipine and Repaglinide in Rats

  • Choi, In;Choi, Dong-Hyun;Yeum, Cheul-Ho;Choi, Jun-Shik
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.498-503
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    • 2011
  • The purpose of this study was to investigate the effects of nisoldipine on the pharmacokinetics of repaglinide in rats. The effect of nisoldipine on cytochrome P450 (CYP) 3A4 activity and P-glycoprotein (P-gp) were evaluated. The pharmacokinetic parameters of repaglinide were also determined in rats after oral (0.5 $mg{\cdot}kg^{-1}$) and intravenous (0.2 $mg{\cdot}kg^{-1}$) administration of repaglinide to rats without or with nisoldipine (0.3 and 1.0 $mg{\cdot}kg^{-1}$). Nisoldipine inhibited CYP3A4 enzyme activity with a 50% inhibition concentration of 5.5 ${\mu}M$. In addition, nisoldipine significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared to the oral control group, nisoldipine significantly increased the $AUC_{0-{\infty}}$ and the $C_{max}$ of repaglinide by 46.9% and 24.9%, respectively. Nisoldipine also increased the absolute bioavailability (A.B.) of repaglinide by 47.0% compared to the oral control group. Moreover, the relative bioavailability (R.B.) of repaglinide was 1.16- to 1.47-fold greater than that of the control group. Nisoldipine enhanced the oral bioavailability of repaglinide, which may be attributable to the inhibition of the CYP3A4-mediated metabolism in the small intestine and/or in the liver and to inhibition of P-gp in the small intestine rather than to reduction of renal elimination of repaglinide by nisoldipine. The increase in the oral bioavailability of repaglinide should be taken into consideration of potential drug interactions when co-administering repaglinide and nisoldipine.

Effects of Amlodipine on the Pharmacokinetics of Warfarin after Oral and Intravenous Administration of Warfarin in Rats

  • Choi, Dong-Hyun;Piao, Yong-Ji;Choi, Eun-Joo;Choi, Jun-Shik;Burm, Jin-Pil
    • 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.

Effects of Hydrocortisone on the Pharmacokinetics of Loratadine after Oral and Intravenous Loratadine Administration to Rats

  • Choi, Jun-Shik;Choi, In;Burm, Jin-Pil
    • Biomolecules & Therapeutics
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    • v.17 no.2
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    • pp.205-210
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    • 2009
  • The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.

The Mechanism of Development of Cyclones in the Area of the Far East Asia (겨울철 극동 아세아의 저기압의 발달기구)

  • 한영호
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.12 no.1
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    • pp.25-30
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    • 1976
  • In the area of the Far East Asia, cyclones are observed 157ea in winter season during the years(1966-1974). Some of them are most difficult to be forecasted due to the extreme irregulalities, have carried out synoptic analysis. The rapid development of cyclones can be attributed to the descending of cold air mass surrounding the axis of the Jet Stream due to the cyclonic rotation, and the lowering of the Jet axis. The Relationships between upper trough line and max. (or min) axis of upper air temperature on the 700mb contributes to the development of the cyclones.

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Quality Characteristics of Noodles Containing Various Levels of Flowering Cherry(Prunus serrulata L. var. spontanea Max. wils.) Fruit Powder (버찌 분말을 첨가하여 제조한 국수의 품질특성)

  • Kim, Sung-Hee;Jung, Bok-Mi
    • Korean journal of food and cookery science
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    • v.29 no.1
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    • pp.19-28
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    • 2013
  • This study was carried out to investigate the quality characteristics and storage of noodle with added flowering cherry fruit powder. Wet noodles were prepared at concentration of 1, 2, and 3% (w/w) of the fruit based on flour weight. Moisture content of the noodles with or without flowering cherry fruit powder was 33.09~33.50%. Ca, K and Mg contents of flowering cherry fruit noodle were increasing at increasing concentrations of flowering cherry fruit powder. Cooked weight, volume, and water absorption decreased with increased fruit powder, whereas turbidity increased. For Hunter's color values of noodles, L (lightness) and b (yellowness) values decreased with increasing concentration of flowering cherry fruit powder, whereas a (redness) value increased. For mechanical characteristics of the noodles, adhesiveness of cooked noodle with flowering cherry fruit powder were higher than those of control. The pH of flowering cherry fruit noodle was lower than that of control during storage. Bacterial counts of wet noodle with flowering cherry fruit powders were lower than those of the control on the 10th day of storage at $5^{\circ}C$. From the sensory evaluation of 20's, texture, taste, and overall preference were not significantly different between the control and the fruit groups, but the color scores of 2% and 3% flowering cherry fruit noodle were significantly higher than that of 1% fruit noodle (p<0.05). In 40's sensory evaluation, color and overall preference scores of flowering cherry fruit noodle were significantly higher than those of control. In conclusion, the results of this study were suggested that the addition of flowering cherry fruit powder in combination with flour was tended to improve antimicrobial effects during storage when compared to control.

Intraspecific Relationship Analysis of Eleutherococcus senticosus Max. by RAPD Markers (RAPD 분석에 의한 가시오갈피의 유연관계 분석)

  • 임정대;성은수;최강준;김승경;김명조;유창연
    • Korean Journal of Plant Resources
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    • v.13 no.2
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    • pp.104-110
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    • 2000
  • To analyse the genetic relationship and intraspecific variations among the Eleutherococcus senticosus population, the polymerase chain reaction(PCR) was performed total genomic DNAs of 10 E. senticosus collections by random 10 primers. The genetic diversity and genetic distance among 10 collections of Eleutherococcus spp. were used to describe the dendrogram showing phylogenic relationship. Ten collections were classfied into two group(group I, II) at the similarity coefficient value of 0.50. Group I included E. senticosus of Bukhado(Japanese), youngwal(Korea), E. seoulense, and E. chiisanesis while group II included several internal and Russia collection. The range of polymorphism was from 66.7 to 90.9% in 87 amplified DNA fragments. The similarity value of all collections ranged from 0.41 to 0.92. The average of genetic distance was 0.61.

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HPLC Determination of Tolperisone in Human Plasma

  • Bae Jung-Woo;Park Young-Seo;Sohn Uy-Dong;Myung Chang-Sun;Ryu Byung-Kwon;Jang Choon-Gon;Lee Seok-Yong
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.339-342
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    • 2006
  • A simple high performance liquid chromatographic (HPLC) method was developed for the determination of tolperisone in human plasma. Tolperisone and internal standard (chlorphenesin) were isolated from 1 mL of plasma using 8 mL of dichlormethane. The organic phase was collected and evaporated under nitrogen gas. The residue was then reconstituted with 300 mL aliquot of mobile phase and a 100 mL aliquot was injected onto the $C_{18}$ reverse-phased column. The mobile phase, $45\%$ methanol containing $1\%$ glacial acetic acid and $0.05\%$ 1-hexanesulfonic acid was run at a flow rate of 1 mL/min. The column effluent was monitored using UV detector at 260 nm. The retention times for tolperisone and the internal standard were approximately 7.1 and 8.4 min, respectively. The standard curve was linear with minimal intra-day and inter-day variability. The quantification limit of tolperisone in human plasma was 10 ng/ mL. The proposed method has been applied to the determination of pharmacokinetic profile of tolperisone in Koreans. The T max of tolperisone in Koreans $(0.94{\pm}0.42\;h)$ was not significantly differ from that reported in Europeans (0.5-1 h), but the mean half-life in Koreans $(1.14{\pm}0.27\;h)$ was shorter than that in Europeans $(2.56{\pm}0.2\;h)$. The proposed HPLC method is simple, accurate, reproducible and suitable for pharmacokinetic study of tolperisone.

Heterologous Expression and Characterization of a Laccase from Laccaria bicolor in Pichia pastoris and Arabidopsis thaliana

  • Wang, Bo;Yan, Ying;Xu, Jing;Fu, Xiaoyan;Han, Hongjuan;Gao, Jianjie;Li, Zhenjun;Wang, Lijuan;Tian, Yongsheng;Peng, Rihe;Yao, Quanhong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2057-2063
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    • 2018
  • Laccases can oxidize a variety of phenolic and non-phenolic substrates including synthetic dyes. In this research, a laccase gene Lcc9 from Laccaria bicolor was chemically synthesized and optimized to heterogeneous expression in Pichia pastoris and Arabidopsis thaliana. The properties of recombinant laccase expressed by P. pastoris were investigated. The laccase activity was optimal at 3.6 pH and $40^{\circ}C$. It exhibited $K_m$ and $V_{max}$ values of $0.565mmol\;l^{-1}$ and $1.51{\mu}mol\;l^{-1}\;min^{-1}$ for ABTS respectively. As compared with untransformed control plants, the laccase activity in crude extracts of transgenic lines exhibited a 5.4 to 12.4-fold increase. Both laccases expressed in transgenic P. pastoris or A. thaliana could decolorize crystal violet. These results indicated that L. bicolor laccase gene may be transgenically exploited in fungi or plants for dye decolorization.

7,8,4'-Trihydroxyisoflavone, a Metabolized Product of Daidzein, Attenuates 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

  • Ko, Yong-Hyun;Kim, Seon-Kyung;Kwon, Seung-Hwan;Seo, Jee-Yeon;Lee, Bo-Ram;Kim, Young-Jung;Hur, Kwang-Hyun;Kim, Sun Yeou;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.363-372
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    • 2019
  • Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

Effect of Ginsenoside Rc on the Pharmacokinetics of Mycophenolic Acid, a UGT1A9 Substrate, and its Glucuronide Metabolite in Rats

  • Park, So-Young;Jeon, Ji-Hyeon;Jang, Su-Nyeong;Song, Im-Sook;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.12 no.2
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    • pp.53-58
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    • 2021
  • Previous in vitro studies have demonstrated that ginsenoside Rc inhibits UGT1A9, but there are no available data to indicate that ginsenoside Rc inhibits UGT1A9 in vivo. The effect of single and repeated intravenous injection of ginsenoside Rc was evaluated on the pharmacokinetics of mycophenolic acid. After injection of ginsenoside Rc (5 mg/kg for one day or 3 mg/kg for five days), 2-mg mycophenolic acid was intravenously injected, and the pharmacokinetics of mycophenolic acid and mycophenolic acid-β-glucuronide were determined. Concentrations of mycophenolic acid and its metabolite from rat plasma were analyzed using a liquid chromatography-triple quadrupole mass spectrometry. Single or repeated pretreatment with ginsenoside Rc had no significant effects on the pharmacokinetics of mycophenolic acid (P > 0.05): The mean difference in maximum plasma concentration (Cmax) and area under the concentration-time curve (AUCinf) were within 0.83- and 0.62-fold, respectively, compared with those in the absence of the ginsenoside Rc. These results indicate that ginsenoside Rc has a negligible effect on the disposition of mycophenolic acid in vivo despite in vitro findings indicating that ginsenoside Rc is a selective UGT1A9 inhibitor. As a result, ginsenoside Rc has little possibility of interacting with drugs that are metabolized by UGT1A9, including mycophenolic acid.