• 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.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.379-383
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• 2000

Stanozolol (STZ, 17$\alpha$-methyl-17$\beta$-hydroxy-5$\alpha$-androstano-(3,2-c) pyrazole), an anabolic steroid, is an abused drug by body-builders or atheletes, as well as medicine for treatment of aplastic anemia and vascular thrombosis. In human volunteers, the major urinary metabolite of STZ was reported to be 3'-hydroxystanozolol that was identified by gas chromatography-mass selective detector (GC/MSD). The objective of this experiment is to investigate the in vitro metabolism of STZ in liver S-9 faction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 faction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100 nmole and the selected time for incubation in the reaction mixture was determined to 60 min. The amount of 3'-hydroxystanozolol produced was increased by about 6-fold in the reaction medium including the liver S-9 fraction of polychlorinated biphenyl-induced rats, compared to that of untreated rats. Inhibitors of cytochrome P450, SKF-525A and 7,8-benzoflavone, decreased the production of 3'-hydroxystanozolol by about 89~100% and 65~75%, respectively; In conclusion, hydroxylation of STZ into 3'-hydroxystanozolol is confirmed by GC/MSD and is catalyzed by cytochrome P450.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.237-242
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• 2011

This study was designed to investigate the effects of glipizide on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Clinically carvedilol and glipizide can be prescribed for treatment of cardiovascular diseases as the complications of diabetes, and then, Carvedilol and glipizide are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of glipizide to rats. The effects of glipizide on cytochrome P450(CYP) 2C9 activity and P-gp activity were also evaluated. Glipizide inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 18 ${\mu}M$. Compared with the control group, the area under the plasma concentration-time curve (AUC) was significantly increased by 33.0%, and the peak concentration ($C_{max}$) was significantly increased by 50.0% in the presence of glipizide after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.13- to 1.33-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of glipizide was increased by 36.8%. After intravenous administration, compared to the control, glipizide could not significantly change the pharmacokinetic parameters of carvedilol. Therefore, the enhanced oral bioavailability of carvedilol may mainly result from inhibition of CYP2C9-mediated metabolism rather than both P-gp-mediated effl ux in the intestinal or in the liver and renal elimination of carvedilol by glipizide.

• Environmental Analysis Health and Toxicology
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• v.7 no.1_2
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• pp.1-16
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• 1992

Biologically, MGK-264 (N-octyl bicycloheptene dicarboximide) acts as a synergists for insecticides mainly pyrethrins and pyrethroids. It's used extensively in combination with pyrethrin and piperonyl butoxide and also with personal insect repellent and cockroach repellents. But the toxic effect of MGK-264 in mamalians was a relatively little known therefore in this studies it was initiated to examine the toxic effect of MGK -264 in rats. For 5 weeks it administrated daily in each 250 mg and 500 mg of MGK-264 per kg of body weight in rats. 1) The body weight gain and the LYMPH (%) value in blood were observed a slight tendency to reduce in accordance with amount of dose and number treatment time. 2) The content of cytochrome P-450 and activity of NADPH-cytochrome c reductase were decreased in liver and those were observed some tendency in the kidney as liver but not significant. 3) The liver cholinesterase activity in the both 250 mg/kg and 500 mg/kg per kg of body weight with treated groups and the liver aniline hydroxylase in 500 mg/kg treated group were gradually decreased from 4 weeks after treated groups. In consequence it would sugested that the toxic effect of MGK-264 was low but in could offer hazard effect in liver and nervers system of rats if it was administrated move dose of MGK-264 and agumented in number of treated time.

• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.262-265
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• 2006

We report a case of phenytoin toxicity due to impaired drug metabolism in a patient homozygous for $CYP2C9^{\ast}3$. A 46-year-old woman was taking phenytoin to prevent postoperative seizures. She attained high serum phenytoin levels at the standard doses (300 mg/day) and developed symptoms of phenytoin toxicity including blurred vision, nausea and headache. The patient was treated with reduced doses of phenytoin and then phenytoin therapy was finally discontinued. Genotyping for CYP2C9 revealed that this patient had a homozygous genotype, $CYP2C9^{\ast}3/^{\ast}3$. This is the first Korean case of phenytoin toxicity with homozygous $CYP2C9^{\ast}3$. This case suggests the clinical usefulness of pharmacogenetic testing for individualized dosage adjustments of phenytoin.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Proceedings of the International Microelectronics And Packaging Society Conference
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• 2003.11a
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• pp.88-93
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• 2003

무전해 Ni-P와 Sn의 반응 및 Ni-P의 결정화에 대한 P 함량의 영향을 세 가지 다른 조성의 Ni-P (P 4.6, 9, 13 $wt.\%$)를 이용하여 연구하였다. $300^{\circ}C$까지 열처리한 모든 시편에서 $Ni_3Sn_4$ intermetallic compound (IMC)가 생성되었고 이들 시편을 $450^{\circ}C$까지 열처리한 경우 Sn 두께가 $0.5{\mu}m$로 작을 때 $Ni_3Sn_4$가 모두 $Ni_3Sn_2$로 변화하였다. nanocrystal인 Ni-4.6P는 Ni (111) texture를 유지하며 결정화되었고 Sn과의 반응시 형성되는 $Ni_3Sn_4$ IMC 또한 비정질인 Ni-9P, Ni-13P 경우보다 강한 (111) texture를 가짐이 확인되었다. Ni-P 막의 P 함량이 작은 경우 $Ni_3Sn_4$ IMC는 두껍고 조밀하게 형성되는 반면 P-rich layer 두께는 작아졌다.

• Korean Journal of Environmental Biology
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• v.21 no.1
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• pp.26-30
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• 2003

Cytochrome P450 (CYP) induction was determined in microsomes of three aquacultured fish species (Sebastes schlegeli, Paralichthys olivaceus and Pagrus major) and two wild fish species (Mugil cephalus and Stephanolepis cirrhifey) in vitro exposed to $\beta$-naphthoflavone (BNF). The microsomes of five fish were exposed to BNF (5 mM or 10 mM) in dimethylsulfoxide at $30^{\circ}C$ for 9 hr. The CYP contents in most fish increased according to exposure duration for 3 or 5 hour, and then decreased, while steady increase of CYP was observed in P. major for 9 hour. The induction of CYP contents in aquacultured fish species (207~422%) were higher than those in wild fish species (206~207%).

• Journal of Marine Life Science
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• v.8 no.2
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• pp.104-114
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• 2023

As plastic usage increases globally, the amount of plastic waste entering the marine environment is steadily rising. Microplastics, in particular, can be ingested by marine organisms and accumulated in their digestive tracts, causing harmful effects on their growth and reproduction. Cytochrome P450 (CYP) enzymes are known to metabolize various environmental pollutants as detoxification enzymes, but their role in crustaceans is not well understood. In this study, sequences of nine CYP genes (CYP370A4, CYP370C5 from clan 2; CYP350A1, CYP350C5, CYP361A1 from clan 3; CYP4AN-like, CYP4AP2, CYP4AP3, CYP4C33-like1 from clan 4) were analyzed using conserved domains in the brackish water flea Diaphanosoma celebensis. Additionally, after exposure to three different sizes of polystyrene beads (0.05-, 0.5-, 6-㎛ PS beads; 0.1, 1, and 10 mg/L) for 48 hours, the expression of these nine CYP genes were investigated using real-time reverse transcription polymerase chain reaction (RT-PCR). The results showed that all CYP genes possessed conserved motifs, indicating that D. celebensis CYP has evolutionarily conserved functions. Among these CYP genes, the expression of CYP370C5, CYP360A1, and CYP4C122 showed a significant increase after exposure to 0.05-㎛ PS beads, suggesting their involvement in PS metabolism. This research will contribute to understanding the molecular mode of actions of microplastics on marine invertebrates.