• Title/Summary/Keyword: drug-interaction

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Protein-Protein Interaction between Poly(A) Polymerase and Cyclophilin A in Chemotactic Cells

  • Choi, Hyun-Sook;Kim, Hana;Lee, Changgook;Kim, Youngmi;Lee, Younghoon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.1
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    • pp.83-86
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    • 2014
  • Poly(A) polymerase (PAP) play an essential role for maturation of mRNA by adding the adenylate residues at the 3' end. PAP functions are regulated through protein-protein interaction at its C-terminal region. In this study, cyclophilin A (CypA), a member of the peptidyl-prolyl cis-trans isomerase family, was identified as a partner protein interacting with the C-terminal region PAP. The interaction between PAP and CypA was inhibited by the immunosuppressive drug cyclosporine A. Deletion analysis revealed that the N-terminal 56 residues of CypA are sufficient for the interaction with PAP. Interestingly, we observed that PAP and CypA colocalize in the nucleus during SDF-1-induced chemotaxis, implying that CypA could be involved in the regulation of polyadenylation by PAP in the chemotactic cells.

Simultaneous Determination of 80 Unapproved Compounds using HPLC and LC-MS/MS in Dietary Supplements

  • Kwon, Jeongeun;Shin, Dasom;Kang, Hui-Seung;Suh, Junghyuck;Lee, Gunyoung;Lee, Eunju
    • Mass Spectrometry Letters
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    • v.13 no.3
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    • pp.58-83
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    • 2022
  • We developed analytical methods using high performance chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 80 unapproved compounds in dietary supplements. The target compounds for analysis were unapproved ingredients (e.g., pharmaceuticals) that have potential adverse effects on consumers owing to accidental misuse, overuse, and interaction with other medication in dietary supplement. Two analytical methods were tested to identify the optimal validation results according to AOAC guideline. As a result, limit of quantification (LOQ) was 0.14-0.5 ㎍ mL-1; linearity (r2) was ≥ 0.99; accuracy (expressed as recovery) was 78.9-114%; precision (relative standard deviation) was ≤ 4.28% in the HPLC method. In the LC-MS/MS method, LOQ was 0.01-2 ng mL-1, linearity (r2) was ≥0.98, accuracy was 71.7-119%; precision was ≤ 12.5%. The developed methods were applied to 51 dietary supplements collected from 2019 to 2021 through MFDS alert system. Based on our previous monitoring study, major compounds were icariin, sibutramine, yohimbine, sildenafil, tadalafil, sennosides (A, B), cascarosides (A, B, C, D), and phenolphthalein. In this study, we re-analyzed samples of detected compounds, and evaluated the statistical difference using Bland-Altman analysis to compare two analytical approaches between HPLC and LC-MS/MS. These results showed a good agreement between two methods that can be used to monitor the unapproved ingredients in dietary supplements. The developed two methods are complementarily suitable for monitoring the adulteration of 80 unapproved compounds in dietary supplements.

Effect of Surfactants on the Solubility Properties of Indomethacin (인도메타신의 용해도에 미치는 계면 활성제의 영향)

  • 김경순;최영혜
    • YAKHAK HOEJI
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    • v.28 no.3
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    • pp.161-167
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    • 1984
  • To improve the solubility properties of indomethacin, a poorly water-soluble drug, some attempts were made with surfactants, such as sodium deoxycholate, sodium laurylsulfate and polysorbate-80. The enhancement effect in solubility was found to be due to the micellar solubilization and dependent on the concentration of surfactants, pH and temperature. The mechanism of interaction was suggested to be attributed to the formation of mixed micelles between the drug and solubilizers.

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Drug Interaction between Nifedipine and Paclitaxel in Rats

  • Kim, Hyung-Jung;Choi, Jun-Shik
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.240.1-240.1
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    • 2003
  • The purpose of this study was to investigate the effect of nifedipine (10 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (50 mg/kg) orally coadministered and pretreated in rats. The plasma concentration of paclitaxel in combination with nifedipine was significantly (p<0.05 at 10 mg/kg coadmin., p<0.01 at pretreat.) increased compared to that of control, from 2 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel with nifedipine was significantly (p<0.05 at 10 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control (omitted)

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Drug-Biomacromolecule Interaction (XIII)-Effect of ionic Strength, pH and Temperature on Binding of Cephalothin to Bovine Serum Albumin- (약물과 생체고분자 간의 상호작용(제 13보)-세파로친과 소혈청알부민의 결합에 미치는 이온강도, pH 및 온도의 영향)

  • Kim, Chong-Kook;Lim, Yun-Su;Yang, Ji-Sun;Jeong, Eun-Ju
    • Journal of Pharmaceutical Investigation
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    • v.19 no.3
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    • pp.163-171
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    • 1989
  • To investigate the protein binding characteristics of cephalothin, the effects of ionic strength, pH and temperature on the binding of cephalothin to bovine serum albumin (BSA) were studied by UV difference spectrophotometric method. With increasing ionic strength at constant PH and temperature, association constant decreased, but the number of binding sites sites was about 2 constantly. It may be deduced that the binding process is not only due to electrostatic forces. And the increased association constant at high ionic strength is explained by conformational changes of BSA from complex to subunits. The pH effect on the affinity of interaction indicated that the binding affinity of drug is higher in the neutral region than in the alkaline region. And, at high pH value, the number of binding sites decreased from 2 to 1 because of the conformational changes of BSA in alkaline region. The decrease in binding affinity of BSA to drug with increasing temperature was characteristic of an exothermic reaction. And the negative sign of ${\Delta}G^{\circ}$ meant that the binding process occurs spontaneously under the experimental conditions. In cephalothin-BSA complex formation, since the net enthalpy change value and entropy change value are positive, it is assumed that hydrophobic bindings are predominant in this binding process.

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Development of Jaspine B analysis using LC-MS/MS and its application: Dose-independent pharmacokinetics of Jaspine B in rats

  • Song, Im-Sook;Jeon, Ji-Hyeon;Lee, Jihoon;Lim, Dong Yu;Lee, Chul Haeng;Lee, Dongjoo;Choi, Min-Koo
    • Analytical Science and Technology
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    • v.34 no.2
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    • pp.37-45
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    • 2021
  • A rapid and simple LC-MS/MS analytical method in determining Jaspine B has been developed and validated in rat plasma. The standard curve value was 25 - 5000 ng/mL and the linearity, inter-day and intra-day accuracy and precision were within 15.0 % of relative standard deviation (RSD). The mean recoveries of Jaspine B ranged from 87.5 % to 91.2 % with less than 3.70 % RSD and the matrix effects ranged from 91.1 % to 108.2 % with less than 2.6 % RSD. The validated LC-MS/MS analytical method of Jaspine B was successfully applied to investigate the dose-escalated pharmacokinetic study of Jaspine B in rats following an intravenous injection of Jaspine B at a dose range of 1 - 10 mg/kg. The initial plasma concentrations and area under plasma concentration curves showed a good correlation with intravenous Jaspine B dose, indicating the dose independent pharmacokinetics of Jaspine B in rats. In conclusion, this analytical method for Jaspine B can be easily applied in the bioanalysis and pharmacokinetic studies of Jaspine B, including its administration at multiple therapeutic doses, or for making pharmacokinetic comparisons for the oral formulations of Jaspine B in small experimental animals as well as in vivo pharmacokinetic-pharmacodynamic correlation studies.

Correlation between the Content and Pharmacokinetics of Ginsenosides from Four Different Preparation of Panax Ginseng C.A. Meyer in Rats

  • Jeon, Ji-Hyeon;Lee, Jaehyeok;Lee, Chul Haeng;Choi, Min-Koo;Song, Im-Sook
    • Mass Spectrometry Letters
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    • v.12 no.1
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    • pp.16-20
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    • 2021
  • We aimed to compare the content of ginsenosides and the pharmacokinetics after the oral administration of four different ginseng products at a dose of 1 g/kg in rats. The four different ginseng products were fresh ginseng extract, red ginseng extract, white ginseng extract, and saponin enriched white ginseng extract prepared from the radix of Panax ginseng C.A. Meyer. The ginsenoside concentrations in the ginseng product and the rat plasma samples were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eight or nine ginsenosides of the 15 tested ginsenosides were detected; however, the content and total ginsenosides varied depending on the preparation method. Moreover, the content of triglycosylated ginsenosides was higher than that of diglycosylated ginsenosides, and deglycosylated ginsenosides were not present in any preparation. After the single oral administrations of four different ginseng products in rats, only four ginsenosides, such as 20(S)-ginsenosides Rb1 (GRb1), GRb2, GRc, and GRd, were detected in the rat plasma samples among the 15 ginsenosides tested. The plasma concentrations of GRb1, GRb2, GRc, and GRd were different depends on the preparation method but pharmacokinetic features of the four ginseng products were similar. In conclusion, a good correlation between the area under the concentration curve and the content of GRb1, GRb2, and GRc, but not GRd, in the ginseng products was identified and it might be the result of their higher content and intestinal biotransformation of the ginseng product.

Evaluation of Interaction and Safety in Administering Herb-medicine with Warfarin (한약과 와파린 병용의 상호작용과 안전성에 대한 연구)

  • Kwon, Dong-Hyun;Kim, Ho-Jun;Lee, Myeong-Jong;Song, Mi-Young
    • Journal of Korean Medicine Rehabilitation
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    • v.20 no.2
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    • pp.175-181
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    • 2010
  • Objectives : The purpose of this study is to investigate interaction and safety in administering herb-medicine with warfarin. Methods : For this study, we selected 19 patients who have been taking warfarin, from the ones that have been transferred from western hospital to oriental hospital. During their stay in the oriental hospital, we gave herb-medicine in addition to warfarin. Then we gathered informations and data on sex, age, main indications, and International Normalized Ratio(INR) values of selected patients through Electronic Medical Records(EMR) of Dong-Guk university hospital. Accordingly, we compiled all of the above data for a period of 10 days prior and 10 days post admission(western hospital period and oriental hospital period, respectively). Results and Conclusions : The statistical analysis of the data have revealed that there was no significant change of INR values after giving herb-medicine with warfarin(p=0.586). The result shows that administration of herb-medicine with warfarin is safe and has little drug interaction. However, this study was carried out on small sample size and the interaction with other drugs and various kinds of herb-medicine was not considered. Although we attained a restrictive result from this study, we are able to suggest the safety about co-administration of herb-medicine and warfarin.

Poly(vinyl pyrrolidone) Conjugated Lipid System for the Hydrophobic Drug Delivery

  • Lee, Hye-Yun;Yu, Seol-A;Jeong, Kwan-Ho;Kim, Young-Jin
    • Macromolecular Research
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    • v.15 no.6
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    • pp.547-552
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    • 2007
  • Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

Drug-Biomacromolecule Interaction XII: Comparative binding study of sulfaethidole to bovine serum albumin by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism

  • Kim, Chong-Kook;Chun, Yang-Sook;Lah, Woon-Lyong
    • Archives of Pharmacal Research
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    • v.12 no.3
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    • pp.160-165
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    • 1989
  • Binding of sulfaethidole to bovine serum albumin was studied by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism. Equilibrium dialysis method enabled us to estimate the total number of drug binding sites of albumin molecule. For sulfaethidole, albumin had 6 primary and 40 secondary binding sites. The primary and secondary binding constants were 0.9 * 10/sup 5/ M/sup -1/ and 0.2 * 10/sup 6/ M/sup -1/, respectivitely. 1-Anilino-8-naphthalenesulfonate (ANS) and 2-(4-hydroxylbenzeneazo)- benzoic acid (HBAB) were used as the fluorescence probe and the uv spectrophotometric probe, respectively. In fluorescence probe technique, results indicated that the number of higher affinity drug binding site of albumin was 1 and the number of lower affinity drug binding sites of albumin was 3, and the primary and secondary drug binding constants for bovine serum albumin were 2.15 * 10/sup 5/M/sup -1/ and 1.04 * 10/sup 5/ M/sup -1/, respectively. In uv difference spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above results suggest that several different methods should be used in ompensation for insufficient information about drug binding to albumin molecule given by only one method.

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