• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4353-4356
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• 2015

Background: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. Materials and Methods: This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM. Conclusions: The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.268-273
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• 2014

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2012년도 제42회 동계 정기 학술대회 초록집
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• pp.540-540
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• 2012

Selective detection of single nucleotide polymorphism (SNP) of Cytochrome P450 2C19 (CYP2C19) was carried out by the PNA chips which were electrically-interfaced with interdigitated nanogap electrodes (INEs). The INEs whose average gap distance and effective gap length were about ~70 nm and ${\sim}140{\mu}m$, respectively, were prepared by the combination of the photo lithography and the surface-catalyzed chemical deposition, without using the e-beam lithography which is almost inevitable in the conventional lab-scale fabrication of the INEs. Four different types of target DNAs were successfully detected and discriminated by the INE-based PNA chips.

• 생명과학회지
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• 제17권3호통권83호
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• pp.334-339
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• 2007

본 연구는 우황청심원을 비롯한 상용되는 20종의 한약제제를 대상으로 9종의 시토크롬 동종효소에 대한 대사능의 저해정도를 고속 스크리닝 기법을 이용하여 탐색함으로써, 한약제제와 약물의 병용으로 인한 약물 상호작용 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 9종의 주요 시토크롬 약물대사효소의 지표약물과NADPH-generating system및 한약제제(500 ${\mu}g/ml$)를 첨가한 후 $37^{\circ}C$에서 15분간 반응시켜 생성된 각각의 대사물을 LC/MS/MS를 이용하여 정량하여 시토크롬 동종효소 활성의 변화를 평가하였다. 그 결과 우황청심원 현탁액 및 황련해독탕 물 추출물이 각각 CYP2B6 및 CYP2D6 효소 활성을 선택적으로 강력하게 저해하였다. 이러한 결과는 약국에서 쉽게 구입할 수 있는 한약제제들 중 일부는 인체 간 시토크롬 활성 저해능을 가지고 있고, 이들 효소에 의해 대사되는 약물과의 병용 복용시 약물상호작용 발생 가능성이 있음을 의미한다. 향후 한약제제에서 저해능을 나타내는 주된 성분을 규명하여 이 성분의 저해능과 저해 기전을 살피는 노력이 필요할 것이다.

• Archives of Pharmacal Research
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• 제28권10호
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• pp.1196-1202
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• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1998년도 제7차 추계학술대회 및 정기총회
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• pp.62-62
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• 1998

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.311-317
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• 2009

Ginkgo biloba (G. biloba) extract is a widely used phytomedicine for the oral treatment of peripheral vascular disease. Cilostazol is a synthetic antiplatelet and vasodilating agent for the treatment of intermittent claudication resulting from peripheral arterial disease. It is likely to use concomitantly G. biloba extract and cilostazol for the treatment of peripheral arterial disease, which raises a concern of increasing their adverse effects of herbal-drug interactions. To clarify any possible herbal-drug interaction between G. biloba extract and cilostazol, the effect of the G. biloba extract on the pharmacokinetics of cilostazol was investigated. As cilostazol is known to be eliminated mainly by cytochrome P450 (CYP)-mediated metabolism, we investigated the effects of G. biloba extract on the human CYP enzyme activities and the effect of G. biloba extract on the pharmacokinetics of cilostazol after co-administration of the two agents to male beagle dogs. The G. biloba extract inhibited more or less CYP2C8, CYP2C9, and CYP2C19 enzyme activities in the in vitro microsomal study with $IC_{50}$ values of 30.8, 60.5, and $25.2{\mu}g/ml$, respectively. In the pharmacokinetic study, co-administration with the G. biloba extract had no significant effect on the pharmacokinetics of cilostazol in dogs, although CYP2C has been reported to be responsible for the metabolism of cilostazol. In conclusion, these results suggest that there may not be a pharmacokinetic interaction between G. biloba extract and cilostazol.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.195-195
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• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• Mass Spectrometry Letters
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• 제7권4호
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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.