• 생물정신의학
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• 제4권1호
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• pp.121-126
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• 1997

본 연구는 정신분열증 환자 38명을 대상으로 하여 haloperidol과 fluoxetine을 8주간 병합투여 하였고, PANSS, CGI, Simpson-Angus 척도를 투여전과 투여후 2, 4, 6, 8주에 시행하여 임상증상 및 추체외로 부작용을 평가하였다. 결과는 다음과 같다. 1) 8주간의 연구기간동안 양성, 음성증상의 유의한 변화가 없었다. 2) 8주의 연구기간동안 추체외로 부작용의 증가가 나타나지 않았다. 이는 기존 연구에서 fluoxetine에 의해 haloperidol의 혈중농도가 증가하여 효과 및 부작용이 증가한다는 연구보고와는 다르며, 이 결과는 haloperidol과 fluoxetine의 병합사용을 안전하게 할 수 있다는 것을 의미한다고 하겠다.

• 생물정신의학
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• 제3권2호
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• pp.251-257
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• 1996

Selective serotonin reuptake inhibitors(SSRIs), as haloperidol, ore metabolized in the cytochrome P450IID6. They can cause inhibition of metabolism of antipsychotics to elevate the serum level of antipsychotics and exacerbate the extrapyramidal symptoms when co-administered with antipsychotics. Among these SSRIs, there ore a few studies about paroxetine compared to fluoxetine or sertraline. In this study, we have intended to know the drug interaction of paroxetine and haloperidol when co-administered two drugs for the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms. for this purpose, we selected 29 subjects, the chronic schizophrenics with no physical problems. They were under maintenance therapy of haloperidol. They ore randomly assigned to placebo group(n=12) and drug group(n=17) by using double blind method. And then, placebo or paroxetine 20mg were administered to the subjects of each groups during 8 week period. We have assessed their psychopathology and extrapyramidal symptoms using Positive and Negative Syndrome Scale(PANSS), Hamilton Rating Scale lor Depression(HRSD), Simpson-Angus Scale at 0, 2, 4, 6, 8 weeks and serum haloperidol, reduced haloperidol levels at 0, 4, 8 weeks during the period. The results ore analysed by using repeated measure MANOVA. 27 subjects have completed the study during 8 weeks. among the subjects, 1) PANSS, HRSD ; no significant difference between groups. 2) Simpson-Angus Scale ; no significant change according to the time and no significant difference between the groups(no group and time effect). 3) Haloperidol and reduced haloperidol level ; no significant change. When co-administered paroxetine and haloperidol, there ore no significant changes of the psychopothology and no significant changes of the extrapyramidal symptoms. In this result, paroxetine seems to be not to affect the metabolism of haloperidol.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.299-304
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• 2003

The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

• 한국임상약학회지
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• 제20권2호
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• pp.99-106
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• 2010

Drugs mostly represent an efficacy or an adverse effect according to their dosage and/or plasma concentrations. Therefore, to investigate the pharmacokinetic behavior of drugs including herbal medicines is necessary both to maximize the drug action and to minimize the adverse effect. To date, pharmacokinetic studies of herbal medicines have been conducted by some experts in this field on the bases of science and knowledge in Korea. On the other hand, in advanced countries, a typical series of pharmacokinetic studies has been conducted by using a harmonized guidance established. Consequently, an administrative support on these studies has to be needed in Korea as well. This study aimed to establish a draft guidance on pharmacokinetic studies of herbal medicines in non-clinical and clinical studies. Literatures previously published as well as guidances in the US, Europe and Japan were summarized for the present guidance. Effect of herbal medicines was listed on the proteins in charge of drug metabolism and transportation, as well as on the pharmacokinetics of chemical drugs. The present suggestion might be helpful to proceed pharmacokinetic studies of herbal medicines efficiently, and further polish should be needed in terms of an administrative point of view.

• 대한의용생체공학회:의공학회지
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• 제38권3호
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• pp.102-110
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• 2017

본 논문은 자석을 회전시켜 실시간으로 자기장을 변화시키고 그로 인해 특정 조건에서 산화철 나노입자를 side point(피부)보다 center point(심부)에서 더 많이 유도할 수 있다는 가능성을 제시하였다. 향후 연구로 유속에 따른 Critical Magnetic flux density, 시간에 따른 나노입자 축적량, 자기장과 산화철 나노입자의 상호작용을 고려한 실험 설계, 전자석 등을 이용한 자기장조절을 연구하여 실질적인 혈관에서 본 실험을 진행할 계획이다.

• Korean Journal of Acupuncture
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• 제23권4호
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• pp.177-186
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• 2006

목적 : 약침액(藥鐵液)의 지질과산화 예방 및 cytocome P450과의 상호 작용에 있어서 대계의 역할은 과거 연구가 거의 없었다. 따라서 본 실험에서는 대계 약침액이 지질과산화를 예방하고, 심혈관계질환 유발에 밀접한 연관이 있는 cytochrome P450의 직접적인 저해 효과를 검토 하고자 한다. 방법 : 대계 약침액이 지질과산화를 억제하는 정도를 평가하기 위하여 세포막을 구성하는 불포화지방산의 일종인 linoleic acid를 대상으로 지질과산화 진행 시간과 대계 약침액의 농도에 의존적인 저해 효과를 실험하였다. 또한 실험쥐의 간조직을 이용하여, 강제적인 과산화를 유도한 후 이를 방어하는 효능을 검토하였다. 그리고 cytochrome P450을 구성하는 그룹의 1A1, 1A2 및 2E1의 활성을 각각 EROD, MROD, p-nitrophenol, aniline 방법으로 측정하였다. 결과 및 결론 : 대계 약침액은 세포막 구성의 불포화 지방산인 linoleic acid의 산화를 시간 및 처리 농도에 의존적으로 억제하였고, 실험쥐의 조직 과산화를 유의성 있게 저해하였다. 또한 aryl hydrocarbon receptor (AHR)을 활성화 시켜 polycyclic aromatic hydrocarbons (PAHs)에 의한 심혈관계 질환 유발 인자로 알려진 cytochrome P450 1A1 및 1A2의 발현을 일부 저해하였으며, 특히 체내에 흡수된 알콜 대사에 관여하는 P450 2E1을 강하게 억제 시켰다.

• 생약학회지
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• 제49권2호
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• pp.85-102
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• 2018

A drug interaction is a situation in which a substance affects the activity of a drug, synergistically or antagonistically, when both are administered together. It has been shown that orally taken ginsenosides are deglycosylated by intestinal bacteria to give ginsenosides metabolites, which has been considered to be genuine pharmacological constituents and to exhibit drug interactions. Animal experimental results demonstrated that ginsenoside metabolites play an important role in the inhibitory or inductive action of both CYPs (cytochrome p450) and P-gp (p-glycoprotein), thereby can be applied as metabolic modulator to drug interactions. Very few are known on the possibility of drug interaction if taken the recommended dose of ginseng, but it has been found to act as CYPs inductor and P-gp inhibitor in any clinical trial, suggesting the risk that side effects will occur. It has been recently reported that interactions might also exist between ginseng and drugs such as warfarin, phenelzine, imatinib and raltegravir. Moreover, medicinal plants are increasingly being taken in a manner more often associated with prescription medicines. Therefore, considering the extensive applications of ginseng for safety, the aim of this review is to present a comprehensive overview of ginseng and drug interactions based upon pharmacodynamic and pharmacokinetic evidences.

• 한국항공운항학회지
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• 제20권1호
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• pp.34-38
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• 2012

호산구는 염증 반응에 의해 활성화되며, 주로 기생충 감염이나 알러지 질환 등에 대한 면역 작용을 담당한다고 알려져 있다. 호산구 증가증은 약물 반응, 알러지, 국소적인 기생충 감염 등에 의한 경우가 많지만, 자가면역성 질환이나 종양에 의한 경우도 있다. 최근 연구를 통해 위염의 대표적인 원인균 중 하나인 유문나선균 역시 위점막에서 나타나는 조직 호산구 증가증의 원인이 될 수 있다고 밝혀지고 있으나, 유문나선균에 의한 호산구 증가증 발생 기전이나 빈도는 아직까지 확립되지 않고 있다. 위점막 내 호산구 침윤과 동반되는 위염은 복통, 오심, 구토, 설사, 장폐색 등을 일으킬 뿐만 아니라, 아토피성 피부염, 천식, 위식도 역류, 염증성 장질환 등의 발생과 관련이 있다고 보고되고 있다. 위염 및 다양한 관련 질환에 의한 증상은 공중 근무자들의 임무 수행 능력을 저하시켜 항공기 사고를 발생시킬 수 있는 가능성을 가지고 있다는 점에서 항공의학적으로 매우 중요하며, 실제로 호산구성 위염이나 유문나선균 감염의 치료 여부가 공중 근무자에게 일시적 또는 영구적 비행임무정지를 부과할 수 있는 기준이 되기도 한다. 본 연구에서는 대한민국 공군 장병 환자를 대상으로 내시경을 통해 얻은 위점막 조직 내 호산구수를 측정하고, 이를 위점막 표면의 유문나선균 존재 유무와 관련지어 보았다. 111명 중 20명의 환자에서 한 고배율 시야 당 30개 이상의 호산구가 관찰되었고, 63명의 환자의 위점막 표면에서 유문나선균을 확인하였다. 또한 위점막 내 호산구의 밀도와 유문나선균의 존재 간의 관계는 통계학적으로 유의하였다. 본 연구의 결과는 대한민국 공군 장병을 대상으로 하여 조직 호산구 증가증과 유문나선균의 빈도 및 상호 관계를 최초로 분석했다는 점에서 의의가 있으며, 추후 유문나선균이 어떤 기전으로 위점막 조직 내 호산구의 증가에 관여하는지에 대한 연구를 진행하기 위한 기초 자료로서 활용될 수 있을 것이다.

• 약학회지
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• 제30권1호
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• pp.42-46
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• 1986

The binding characteristics of five cephalosporins, cefamandole, ceftriaxone, cefoxitin, latamoxef, and cefotetan to bovine serum albumin (BSA) was examined by UV difference spectrophotometry. 2-(4'-hydroxybenzeneazo) benzoic acid was used as the spectrophotometric probe. Competitive bindings between the probe and cephalosporins were observed. Based on the Scatchard plot, the BSA appeared to have two classes of binding sites in BSA binding with cephalosporins. The number of primary binding sites appears to be one, secondary binding sites appears to be three. The binding constants were found as follows: BSA-HBAB; $K_1^{obs}$=8.39$\times$$10^4$ $M^{-1}$, $K_2^{obs}$=1.60$\times$$10^4$ $M^{-1}$, BSA-Cefamandole; $K_1^{obs}$=5.44$\times$$10^3$ $M^{-1}$, $K_2^{obs}$=0.74$\times$$10^3$ $M^{-1}$, BSA-Cefotriaxone; $K_1^{obs}$=6.78$\times$$10^3$ $M^{-1}$, $K_2^{obs}$=0.88$\times$$10^3$ $M^{-1}$, BSA-Cefoxitin; $K_1^{obs}$=7.24$\times$$10^3$ $M^{-1}$, $K_2^{obs}$=1.13$\times$$10^3$ $M^{-1}$, BSA-Latamoxef; $K_1^{obs}$=8.87$\times$$10^3$ $M^{-1}$, $K_2^{obs}$=1.92$\times$$10^3$ $M^{-1}$, BSA-Cefotetan; $K_1^{obs}$=15.41$\times$$10^3$ $M^{-1}$, $K_2^{obs}$=2.7$\times$$10^3$ $M^{-1}$.

• 한국임상약학회지
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• 제20권1호
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.