• 한국임상약학회지
• /
• 제23권3호
• /
• pp.239-247
• /
• 2013

Background: Fixed drug combinations are formulations containing two or more active ingredients in a single dosage form. Such combination therapies are commonly applied to improve efficacy, reduce adverse events and replace co-administration, etc. National and international guidelines for hypertension treatment recommend addition of other classes of antihypertensive drugs rather than incremental dose of mono-therapy, when blood pressure is not adequately controlled. Thus, many dual combinations of antihypertensive drugs have been approved and pharmaceutical companies are recently interested in developing antihypertensive triple combinations. Clinical trial designs for the fixed combinations are various depending on the target patients, dosage and clinical endpoints. Thereby, further discussions for the clinical trials of antihypertensive triple therapies are required regarding the indication claimed. Conclusion: This article provides a review for the assessment of the label and medical reports of the clinical trials on antihypertensive triple therapies in advanced foreign countries.

• 한국근적외분광분석학회:학술대회논문집
• /
• 한국근적외분광분석학회 2001년도 NIR-2001
• /
• pp.3111-3111
• /
• 2001

The implementation of NIR and chemometrics in the Pharmaceutical industries is still in strong progress, both regarding qualitative and quantitative applications and beneficial results are seen. Looking at the development so far, NIR will change the pharmaceutical industry even more in the future. This presentation will address the experiences and progress achieved regarding the application and implementation of quantitative methods for determination of content uniformity and assay of tablets with less than 10% w/w of active, using Near Infrared transmittance spectroscopy in combination with PLS. Also qualitative methods for identification of the same tablets by Near Infrared reflectance spectroscopy will be discussed. Four commercial tablet strengths are formulated and produced from two different compositions by direct compression. Three different strengths are dose proportional, i.e. fixed concentration by varying in size. The aim was to replace the conventional primary methods for analysing content uniformity, assay and identification by NIR. Studies were performed on comparing transmittance versus reflectance spectroscopy for both applications on the dose proportional tablets. The model for determination of content uniformity and assay was developed to cover both coated and uncoated tablets, whereas the qualitative model was developed to identify coated tablets only. The impact of the tablet formulation, tablet size and coating, resulted in individual models far each composition The best calibration was achieved using diffuse reflectance for the identification purposes and diffuse transmittance for the quantitative determination of the active content within the tablets. As NIR in combination with other techniques opens up the possibility of total quality management within the production, the transfer of the above-mentioned models from a laboratory based approach to an at-line approach at H.Lundbeck will be addressed too.

• Parasites, Hosts and Diseases
• /
• 제40권1호
• /
• pp.1-7
• /
• 2002

The purpose of treatment for uncomplicated malaria is to produce a radical cute using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg/day) for 3 days; a fixed dose of artemether and lumefantrine (20/120 mg tablet) named $Coartem^{\circledR}$ (4 tablets twice a day for three days for adults weighing more than 35 kg); quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over; $Malarone^{\circledR}$ (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then dialy for 5 days; arteether i. m. ($Artemotil^{\circledR}$) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days. Oral arlemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.

• 대한의용생체공학회:의공학회지
• /
• 제28권6호
• /
• pp.756-767
• /
• 2007

For the combination of phosphor screens having various thicknesses and a photodiode array manufactured by complementary metal-oxide-semiconductor (CMOS) process, we report the observation of image-quality degradation under the irradiation of 45-kVp spectrum x rays. The image quality was assessed in terms of dark pixel signal, dynamic range, modulation-transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). For the accumulation of the absorbed dose, the radiation-induced increase both in dark signal and noise resulted in the gradual reduction in dynamic range. While the MTF was only slightly affected by the total ionizing dose, the noise power in the case of $Min-R^{TM}$ screen, which is the thinnest one among the considered screens in this study, became larger as the total dose was increased. This is caused by incomplete correction of the dark current fixed-pattern noise. In addition, the increase tendency in NPS was independent of the spatial frequency. For the cascaded model analysis, the additional noise source is from direct absorption of x-ray photons. The change in NPS with respect to the total dose degrades the DQE. However, with carefully updated and applied correction, we can overcome the detrimental effects of increased dark current on NPS and DQE. This study gives an initial motivation that the periodic monitoring of the image-quality degradation is an important issue for the long-term and healthy use of digital x-ray imaging detectors.

• The Korean Journal of Pain
• /
• 제18권1호
• /
• pp.10-14
• /
• 2005

Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the $ED_{50}$ for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. $ED_{50}$ of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.

• Toxicological Research
• /
• 제16권3호
• /
• pp.195-200
• /
• 2000

Antidotal efficacy of physostigmine plus procyclidine, the combinational prophylactics for organophosphate poisoning, was evaluated in rats and guinea pigs. To assess the dose-response relation-ship in rats, various doses (0.3-6.0mg/kg) of procyclidine in combination with a fixed dose (0.1mg/kg) of physostigmine were pretreated subcutaneously 30 min prior to subcutaneous exposure to nerve-agents. Physostigmine alone exerted protection ratios of 2.44, 1.20, 1.50, 1.50 and 2.20 folds for tabun, sarin, soman, cyclosarin and V-agent, respectively. Interestingly, coadmnistration of procyclidine with physostigmine exhibited remarkable synergistic effects in a dose-dependent manner, leading to 4.00~8.00 folds for tabun, 2.15-8.50 folds for sarin, 1.92~507 folds for so man, 2.15~2.90 folds for cyclosarin, and 2.71~10.50 folds for V-agent. On the contrary, a low effect (l.65 fold) was achieved with the traditional antidotes atropine (17.4 mg/kg) plus 2-pralidoxime (30 mg/kg) treated immediately after soman poisoning. Noteworthy, the combinational prophylactics markedly potentiated the effect of atropine plus 2-pralidoxime to 6.13 and 12.27 folds with 1.0 and 3.0 mg/kg of procyclidine, respectively, against soman poisoning. In guinea pigs, the physostigmine plus procyclidine prophylactics exerted protective effects of 3.00~4.70 folds against soman intoxcation, which were much higher at low doses (0.3~1.0 mg/kg) of procyclidine than those in rats. Taken together, it is proposed that the combinational prophylactics composed oj physostigmine and procyclidine could be a promising antidote regimen for the poisoning with organophosphates possessing diverse properties.

• Radiation Oncology Journal
• /
• 제4권2호
• /
• pp.165-172
• /
• 1986

전자선 치료시에 납판이나 저융점 합금이 조사면의 형태의 변형을 위하여 사용되고 있다. 콜리메이팅 장치와 마찬가지로 조사면 변형을 위한 물질도 전자선의 출력에 영향을 미친다. 저자들은 폴리스티렌 팬톰에 삽입된 Farmer형 전리함을 이용하여 Clinac-18의 전자선의 변형된 조사면에 대한 출력율을 측정하고 출력율에 영향을 미치는 요인들에 관해 분석했다. 전자선의 출력율은 전자선의 초기 에너지, 콜리메이팅 장치뿐만 아니라 조사면 크기에도 좌우되었다. 변형된 조사면에 대하여 잔자선의 에너지에 관계없이 X-선 콜리메이터와 전자선 어플리케이터의 조합이 고정되면 조사면의 크기 대 출력율은 A/P로 표시된 등가조사면의 크기에 따라 변하지만 조사면의 형태에 대해서는 무시할 수 있었다. 그러나 개조사면에 대한 출력율은 변형조사면의 출력율로부터 예상될 수 없고, 그것들만의 독립적인 관계를 가지고 있었다. 어플리케이터와 콜리메이터의 조합이 고정된 경우에 한해서 판자선의 변형조사면에 대한 출력율은 A/P로서 표시된 등가 조사면 방법에 의하여 구할 수 있다.

• 치과방사선
• /
• 제22권2호
• /
• pp.293-303
• /
• 1992

Generally the patient's absorb dose and readability of radiograms are affected by the exposure time and kVp of which are related with the radiographic density and contrast The investigator carried studies to know the adequate level of exposure time and kVp to obtain the better readability of radiograms. In these studies dried human mandible with selfcuring acrylic resins attached with aluminum step wedge was used and readability of radiograms were compared with each other by videodensitometry among various combination sets of the exposure time, such as 5, 6, 8, 12, 15, 19, 24, 30, 38, 48 and 60, and varing level of kVp, such as 60, 65, 70, 80 and 90 respectively. The obtained results were as follows: 1. As exposure time and kVp were increased, radiographic density of radiograms was increased. 2. The subject contrast was increased where aluminum step wedge was thin and reduced in the reversed condition. At the thin aluminum step wedge, subject contrast was increased at the condition of lower kilovoltage than that of higher kilovoltage. 3. In the case of non-constant radiographic density, the radiographic contrast was reduced with the increment kilovoltage. The radiographic contrast was increased in the lower kilovoltage with the longer exposure time and the higher kilovoltage with the shorter exposure time. 4. At the condition of short exposure time, better readability of each reading item was obtained with the increment of the kilovoltage but at the opposite condition increasing exposure time worsened readability of radiograms. Since X-ray machine in the current dental clinics is fixed between the range of 60-70kVp and 10mA, good radiograms can be obtained by varied exposure time. But according to the conclusion of these studies, better radiograms can be obtained by using filtered high kVp and then the absorb dose to patient and exposure time can be reduced.

• 한국축산식품학회지
• /
• 제24권2호
• /
• pp.198-201
• /
• 2004

천연발효물질인 프로폴리스를 이용하여 숙취 해소 음료를 개발하고 그에 따른 알콜 대사에 미치는 효과를 알아보고자 하였다. 프로폴리스 농축액과 다양한 약용식물의 농축액을 사용하여 숙취 해소 음료를 개발하였다. 배합원료 각각의 알콜 분해 능력을 검토한 결과, 프로폴리스와 가시오가피 추출액이 가장 큰 분해 능력을 보였다. 타 회사 제품과의 알콜 분해 능력을 비교한 경우 급성 주정 중독량 (kg당 4g)을 경구 투여하였을 때 유의적인 차이를 보이지 않았다. 그러나 주정중독량 지표보다 약 1/3을 감소시킨 kg당 1.8 L의 술을 경구 투여한 경우, 프로폴리스 음료는 270분이 경과했을 때 0.026%, 360분이 경과했을 때에는 0.000%의 혈중알콜농도를 나타내었다. 이것으로 보아 프로폴리스 음료는 섭취알콜의 양이 많을 경우에는 큰 차이가 없었지만, 일정량의 알콜을 섭취할 경우에는 매우 뛰어난 알콜 분해 효능이 있음을 알 수 있었다.

• 한국임상약학회지
• /
• 제27권3호
• /
• pp.150-160
• /
• 2017

Background: Recently, a fixed combination of grazoprevir and elbasvir (GE) has been introduced to the arsenal of chemotherapeutics to fight against this virus. The study aimed to provide information on the efficacy and safety of GE for the treatment of HCV infection by performing a meta-analysis of literature data. Methods: PubMed and EMBASE database searches were conducted. Among the literature retrieved, pivotal Phase III clinical studies were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal Phase III clinical studies compared the efficacy and safety of GE. When HCV patients were treated with GE for 12 weeks, the sustained virologic response, defined as the viral RNA level below the lower limit of quantification at 12 weeks after the cessation of therapy (SVR12), was 94.7%. The clinical advantage of GE involves its use by patients with cirrhosis and/or renal failure without dose adjustment. If the genotype (GT) of the causative virus was GT1a with NS5A polymorphism or GT4 with resistance to peginterferon/ribavirin, treatment with GE plus ribavirin for 16 weeks resulted in a better outcome compared to treatment with GE alone for 12 weeks. Adverse events reported during the four clinical studies were 71.09% in the GE arms and it was 76.61% in the non-GE arms, with the most frequent events being mild central nervous system symptoms. Conclusion: GE was generally safe and effective for the treatment of HCV infection. However, since HCV mutates very rapidly and becomes resistant to antiviral agents, long-term monitoring should be mandatory.