• Title/Summary/Keyword: Drug Effect

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The Effect of Drug Vintage on Mortality : Economic Effect of New Drug (약의 허가시점분포가 사망률에 매치는 영향 : 신약의 거시경제적 효과)

  • Jung, Kee-Taig;Kim, Jeong-Yoon;Lichtenberg, Frank
    • Health Policy and Management
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    • v.16 no.4
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    • pp.147-168
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    • 2006
  • Technological innovation has been regarded as the core competence for the economic growth of individual, as well as organization and country. Pharmaceutical innovation, what we call new medicines, influence people's longevity and productivity by increasing output per hour worked. Therefore, using claims data on virtually all the drugs and diseases of over 550,000 people enrolled in National Health Insurance Program in Korea, we examined the impact of the vintage (original FDA and KFDA approval year) of drugs used to treat a patients from July 1st to December 31st in 2002 on the patient's mortality at the end of 2004, controlling for demographic characteristics(age and sex), utilization of medical services, and the nature and complexity of illness. We found that people using newer drugs are less likely to die at the end of 2004, conditional on covariates. The estimated mortality rates were declining with respect to drug vintage for 1970s, 1980s and 1990s and highly significant. In addition to estimating the model for the entire sample, we estimated the model separately for several disease categories classified by Korean Classification of Disease. Estimates of three drug vintage variables for subgroups of people with (1)neoplasms, (2)endocrine, nutritional and metabolic diseases, and (3)the diseases of circulatory system displayed similar patterns.

The Optimization of Method for Prediction of Drug-Induced Liver Injury Using HepG2 Cells Cultured with Human Liver Microsomes (Human Liver Microsomes과 HepG2 세포를 이용한 약물유래 간독성 평가 방법의 최적화)

  • Choi, Jong Min;Jeon, Jang Su;Kim, Sang Kyum
    • YAKHAK HOEJI
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    • v.59 no.5
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    • pp.201-206
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    • 2015
  • The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

Effect of Vitamin A and $B_2$ Derivatives on Aminopyrine Demethylase Activity (비타민 A 및 $B_2$ 유도체의 Aminopyrine Demethylase 활성도에 대한 영향)

  • 이향우
    • YAKHAK HOEJI
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    • v.28 no.1
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    • pp.53-59
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    • 1984
  • Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

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Food-Effect Bioavailability and Fed Bioequivalence Studies (생체이용률에 미치는 음식물의 영향 및 식후 생물학적동등성시험)

  • Choi, Sun-Ok;Kwon, Kwang-Il;Jung, Sung-Hee;Um, So-Young;Jung, Seo-Jeong;Kim, Joo-Il;Chung, Soo-Youn;Kim, Ok-Hee
    • Korean Journal of Clinical Pharmacy
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    • v.15 no.2
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    • pp.82-88
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    • 2005
  • A new medical system was started in Korea in 2000 and pharmaceutical affairs law was revised in 2001. According to the revised law, generic substitution is permitted only to therapeutically equivalent generic product. Bioequivalence studies are usually used to demonstrate therapeutic equivalence between reference listed drugs and generic drugs. The issues that are recently heating up in Korea are to increase bioequivalent drug products and at the same time to ensure the credibility of the therapeutic equivalence of generic drugs. Sometimes food can change the bioavailability (BA) of a drug and influence the bioequivalence (BE) between test and reference products as well. Food effects on BA can have clinically significant consequences. Food can alter BA by various means including delaying gastric emptying, stimulating bile flow and changing gastointestinal pH. This paper provides the recently published Korean guideline on food-effect BA and fed BE studies.

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The effect of drug holiday before tooth extraction on the development of medication-related osteonecrosis of the jaw in cancer patients receiving intravenous bisphosphonates

  • Cigdem Karaca;Goknur Topaloglu-Yasan;Selen Adiloglu;Ecem Usman
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.49 no.2
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    • pp.68-74
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    • 2023
  • Objectives: Drug holidays are suggested to reduce the formation of osteonecrosis in patients under intravenous (IV) bisphosphonates (BPs) therapy. The objectives of this study are to evaluate the incidence of medication-related osteonecrosis of the jaw (MRONJ) following tooth extraction in cancer patients using IV BP, and to assess the effect of drug holiday on the development of MRONJ. Patients and Methods: A manuel search of the patient folders of Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hacettepe University was undertaken to identify cancer patients who used IV BPs and had at least one tooth extraction between 2012 and 2022. Patents' age, sex, systemic condition, the type of BP used, duration of BP used, number of tooth extraction, duration of drug holiday, localization of tooth extraction and incidence of MRONJ were recorded. Results: One hundred nine teeth were removed from 57 jaws in 51 patients. All tooth extractions were performed under perioperative antibiotic prophylaxis and with primary wound closure. The incidence of MRONJ was 5.3%. Stage 1 MRONJ developed in 3 patients (only one had a drug holiday). The median duration of drug holiday was 2 months. No significant difference between the patients with and without a drug holiday and MRONJ development was found (P=0.315). The mean age of patients developed MRONJ was 40.33±8.08 years. A statistically significant difference was found between age and MRONJ development (P=0.002). Conclusion: The effect of a short-term drug holiday on the development of MRONJ may be limited because BPs remain in bone tissue for a long time. Drug holidays should be applied with the approval of an oncologist with other preventive measurements.

Transdermal Permeation of Xanthan Gum Bases on the Water-soluble and Lipophilic Antihyperlipoproteinemic Drugs (수용성과 지용성 항고지단백혈증제에 대한 Xanthan Gum 기재에서의 경피투과)

  • 이석우;임윤택;공승대;황성규;이우윤
    • KSBB Journal
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    • v.16 no.3
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    • pp.253-258
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    • 2001
  • Recently, there were many studies not only to enhance drug delivery effect but to reduce side effect. Drug delivery system(DDS) is able to improve efficiency with decreasing side effect of drug dosage. Among these application fields, DDS is often used as the method of drug dosage into the epidermic skin. We investigated characters of transdermal therapeutic system(TTS) and the skin permeability of that with applying DDS. We investigated the permeation of xanthan gum containing drug in rat skin using borizontal membrane cell model. Permeation properties of materials were investigated for water-soluble drug with oxiniacic acid and also for lipophilic drug with clofibrate. The permeation rate of lipophilic drug was found to be faster than that of water-soluble drug in vitro. The rate differences of both water-soluble drug and lipophilic drug according to drug content were negligible. We used glycerin, PEG 600 and oleic acid as enhancers. These results showed that skin permeation rate of each drug across the composite was mainly dependent on the property of base and chemical property of drug etc.. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate. This result suggests a possible use of natural polymer base as a transdermal delivery system of antihyperlipoproteinemic agent.

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Effect of Enterotoxigenic Escherichia coli on Microbial Communities during Kimchi Fermentation

  • Lee, Woojung;Choi, Hyo Ju;Zin, Hyunwoo;Kim, Eiseul;Yang, Seung-Min;Hwang, Jinhee;Kwak, Hyo-Sun;Kim, Soon Han;Kim, Hae-Yeong
    • Journal of Microbiology and Biotechnology
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    • v.31 no.11
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    • pp.1552-1558
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    • 2021
  • The diverse microbial communities in kimchi are dependent on fermentation period and temperature. Here, we investigated the effect of enterotoxigenic Escherichia coli (ETEC) during the fermentation of kimchi at two temperatures using high-throughput sequencing. There were no differences in pH between the control group, samples not inoculated with ETEC, and the ETEC group, samples inoculated with ETEC MFDS 1009477. The pH of the two groups, which were fermented at 10 and 25℃, decreased rapidly at the beginning of fermentation and then reached pH 3.96 and pH 3.62. In both groups, the genera Lactobacillus, Leuconostoc, and Weissella were predominant. Our result suggests that microbial communities during kimchi fermentation may be affected by the fermentation parameters, such as temperature and period, and not enterotoxigenic E. coli (ETEC).

Effect of Sarcotride A on Membrane Potential in C6 Glioma Cells

  • Lee Yun-Kyung;Liu Yong-Hong;Jung Jee-H.;Im Dong-Soon
    • Biomolecules & Therapeutics
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    • v.14 no.2
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    • pp.110-113
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    • 2006
  • We tested effect of sarcotride A, a bioactive cyclitol derivative from a marine sponge, on membrane potential in C6 glioma cells. Membrane potential was estimated by measuring fluorescence change of DiBAC-loaded glioma cells. Sarcotride A increased membrane potential in a concentration-dependent manner. We tested effects of pertussis toxin, U73122, EIPA, and $Na^+-free$ media on sarcotride A-induced increase of membrane potential to investigate involvement of G proteins, phospholipase C, $Na^+/H^+$ exchanger, and $Na^+$ channels. However, we were not able to observe any significant effect of those pharmacological inhibitors, excluding the involvement of the molecules as candidate targets or signaling molecules of sarcotride A-induced increase of membrane potential. Further investigation is necessary to elucidate action mechanism of sarcotride A.

Effect of Scutellariae Radix Extract on Human CYP450 Mediated-Drug Metabolism

  • Yoo, Hye-Hyun;Lim, Sun-Young;Kim, Dong-Hyun
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.143-146
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    • 2011
  • Scutellariae Radix is widely used in the traditional herbal medicine for the treatment of fever, cough, dysentery, hepatitis and hypertension in Korea, China and Japan. In this study, we investigated the effects of 70% ethanolic extract of Scutellariae Radix (SRE) on CYP450-mediated drug metabolism in the in vitro systems using human liver microsomes and hepatocytes. The microsomal incubation assay showed that SRE inhibited the drug metabolism reactions catalyzed by CYP1A2, CYP2C8 and CYP2C9 in a dose-dependent manner. In particular, SRE was shown to strongly inhibit the metabolic activity of CYP1A2 with an $IC_{50}$ value of 4.6 ${\mu}g/mL$. When SRE was evaluated for its effect on the induction of CYP450 enzyme activities in cryopreserved human hepatocytes, SRE did not exhibit any effect.