• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.106-114
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• 2011

While multiple medication is an important global medication safety issue, ununified concomitant medication by multiple prescriptions may cause more severe problems by the fact that those are neither intended nor watched. This could cause therapy duplication and severe drug interaction and etc. Korean Government made region wide scale programs twice to detect such problems and give warnings to pharmacists and doctors through the internet system in 2009-2010, which are called Drug Use Review Services Pilot Project. This study is an analysis and comparison of the results of the two DUR pilot projects. There were 5.0 and 4.2 cases of severe drug interaction by the concomitant medication of multiple doctors' prescriptions per 10 thousand prescriptions, while only 0.37 and 0 cases by the medication of same doctor's prescription(s). There were 426 and 381 cases of drug duplication by the concomitant medication of multiple doctors' prescriptions per 10 thousand cases, while only 197 and 23 cases by medication of same doctors' prescription(s). Doctors' participation to those projects improved at Jejudo the later one compared to Goyangsi the former, which means the efforts of them to make less prescription problems succeeded to decrease the number of cases caused from same doctor's prescription. But they could not decrease the number of problem cases caused from concomitant medication by multiple doctors prescriptions enough. The findings support the issue of strengthening and widening the project nation wide and the issue of recommending the patients to designate their own pharmacy, which can provide them counseling for unified and safety controlled medication.

• YAKHAK HOEJI
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• v.57 no.3
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• pp.194-198
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• 2013

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2722-2726
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• 2011

Plasticized poly(vinyl chloride), PVCs, with different membrane compositions tested for use in the construction of an ion-selective sensor for the determination dibucaine. A prepared membrane with dioctyl phthalate-PVC and ion-pair of N-(1-naphthyl)ethylenediamine dihydrochloride-tetraphenyl borate had a good potential to acts as a potentiometric sensor for the analysis of dibucaine. A linear relationship was obtained between potential and logC varying between $1.0{\times}10^{-6}$ and $1.0{\times}10^{-2}$ M dibucaine with a good repeatability and reproducibility. The sensor was applied for the determination of the drug in pharmaceuticals and biological fluids such as plasma and urine samples with satisfactory results. The drug electrode has also been used to study the interaction of bovine serum albumin (BSA) with dibucaine. The saturated quantities of dibucaine binding were 13.04, 5.30 and 9.70 mol/mol in 0.01, 0.02 and 0.1% of protein, respectively.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.265-269
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• 2002

The purpose of this study was to report the pharmacokinetic changes of cyclosporine after oral administration of cyclosporine, 10 mg/kg, in rabbits coadministered or pretreated twice per day for 3 days with nimodipine, dose of 5 mg/kg. The area under the plasma concentration-time curve (AUC) of cyclosporine was significantly higher in rabbits pretreated with nimodipine than that in control rabbits (p＜0.01), showing about 149％ increased relative bioavailability. The peak plasma concentration (C$_{max}$), elimination half-life (t$_{1}$2/) and MRT of cyclosporine were increased significantly (p＜0.05) in rabbits pretreated with nimodipine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant and total body clearance by pretreated with nimodipine. The effects of nimodipine on the pharmacokinetics of oral cyclosporine were more considerable in rabbits pretreated with nimodipine compared with those in control rabbits. The results suggest that the dosage of cyclosporine should be adjusted when the drug would be coadministered chronically with nimodipine in a clinical situation.n.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.2
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• pp.219-230
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• 1992

Nutrients and drugs are similar to biological fate, such as absorption, metabolism and excretion. Such procedure may interact with nutrients and drugs. Drugs can influence nutrient absorption, metabolism or excretion ; the effects may impair the nutritional status of a patient. Specific nutrient, nutritional status, or dietary factors alter drug utilization. Therefore, medicated patients need to be aware of good nutrition practices and to understand the importance of dietary modifications associated with certain diseases. A nutritious and well balanced diet not only makes an important contribution to the health of those patients, but also reduces the risk of nutrition disorders or altered the pharmacological action of drugs.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.19-24
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2004.05a
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• pp.19-24
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• 2004

• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.90-95
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• 2016

Heat Shock 70kDa Protein 1-Like(HSPA1L)는 Heat-shock protein70(HSP70) family에 속하는 chaperone protein으로 polypeptide folding, assembly, protein degradation 등 다양한 biological processes에 관여하고 있다. HSPA1L은 human methyltransferase-like protein 21A(METTL21A)에 의해 lysine residue에 methylation이 일어나게 되는데, 암세포에서 일반적인 HSPA1L은 주로 세포질에서 발견되는 반면 methylated HSPA1L의 경우 주로 핵에서 발견이 됨으로써 HSPA1L methylation이 암 세포 성장에 중요할 역할을 할 것이라 추측되며 anti-cancer drug target으로 주목 받고 있다. 하지만 현재 HSPA1L의 구조가 부분적으로만 밝혀져 있어 HSPA1L와 METTL21A가 어떤 residue들이 interaction 하여 binding을 하는지에 대해서 아직 밝혀 지지 않았다. 이로 인해 anti-cancer drug target으로서의 연구에 제한이 있다. 이번 연구에서는 homology modeling(Galaxy-TBM, Galaxy-refine)을 통해 HSPA1L 전체 구조를 밝혀 낸 후, HSPA1L 와 METTL21A를 protein-protein docking을 통해 binding pose 예측을 하였다. 이러한 binding pose를 protein interaction analysis하여 HSPA1L과 METTL21A binding에 관여하는 중요 residue들을 밝혀 냈다. 이러한 structural information은 methylated HSPA1L와 암 세포 성장간의 연관성, 더 나아가 anti-cancer drug 개발로 까지도 이어 질 수 있을 것이라 생각한다.

• Genomics & Informatics
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• v.21 no.1
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• pp.6.1-6.8
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• 2023

Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.