• Title/Summary/Keyword: Drug Distribution

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Pharmacokinetic Behavior and Biodistribution of Paclitaxel-Loaded Lipid Nanosuspension

  • Choi, Sung-Up;Park, Jung-Min;Choi, Woo-Sik;Lee, Jae-Hwi;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.359-366
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    • 2009
  • In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol$^{(R)}$ performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol$^{(R)}$, but the reduced release profile for PxLN-C. PxLN or Taxol$^{(R)}$ was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC$_t$ of PxLN-H was 3.4-fold greater than that of Taxol$^{(R)}$. PxLN-H gave higher biodistribution in all tissues than did Taxol$^{(R)}$. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

Physicochemical Characterization and Carcinoma Cell Interaction of Self-Organized Nanogels Prepared from Polysaccharide/Biotin Conjugates for Development of Anticancer Drug Carrier

  • Park Keun-Hong;Kang Dong-Min;Na Kun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.9
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    • pp.1369-1376
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    • 2006
  • Self-organized nanogels were prepared from pullulan/biotin conjugates (PU/Bio) for the development of an effective anticancer drug delivery system. The degree of biotin substitution was 11, 19, and 24 biotin groups per 100 anhydroglucose units of pullulan. The physicochemical properties of the nanogels (PU/Bio1, 2 and 3) in aqueous media were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of all the samples was less than 300 nm with a unimodal size distribution. The critical aggregation concentrations (CACs) of the nanoparticles in distilled water were $2.8{\times}10^{-2},\;1.6{\times}10^{-2}$, and $0.7{\times}10^{-2}mg/ml$ for the PU/Bio1, 2, and 3, respectively. The aggregation behavior of the nanogels indicated that biotin can perform as a hydrophobic moiety. To observe the specific interaction with a hepatic carcinoma cell line (HepG2), the conjugates were labeled with rhodamine B isothiocyanate (RITC) and their intensities measured using a fluorescence microplate reader. The HepG2 cells treated with the fluorescence-labeled PU/Bio nanoparticles were strongly luminated compared with the control (pullulan). Confocal laser microscopy also confirmed internalization of the PU/Bio nanogels into the cancer cells. Such results demonstrated that the biotin in the conjugate acted as both a hydrophobic moiety for self-assembly and a tumor-targeting moiety for specific interaction with tumor cells. Consequently, PU/Bio nanogels would appear to be a useful drug carrier for the treatment of liver cancer.

Analysis and exposure assessment of the total PCBs in foods (식품 중 총 PCBs의 분석 및 노출량 평가)

  • Oh, Keum Soon;Suh, Junghyuck;Paek, Ock Jin;Kim, Dongsul
    • Analytical Science and Technology
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    • v.22 no.6
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    • pp.449-457
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    • 2009
  • Total PCBs (62 congeners) has been determined in the retailed foods by the isotopic dilution method and the exposure assessment has been performed. Put into a food sample $^{13}C$-labeled standard for recovery was added and then it was extracted, cleaned-up by multi-layer column chromatography and then analyzed by HRGC/MS. The average levels (ng/g) detected was 0.1 for rice, 1.8~3.4 for meats, 0.3~3.7 for milk and dairy products, 10.0 for egg and 0.8~34.4 for fishes. Distribution of total PCBs was in order of fishes (94.4%) > meats (2.3%) > eggs (1.7%) > milk and dairy products (1.3%) > rice (0.3%). The estimated daily intake(EDI) was 14 ng/kg bw/day. It was concluded that there was no health risk at all.

Effects of Nutrition Therapy and Drug Treatment on the Blood Lipid Levels in Patients with Hyperlipidemia according to Genetic Polymorphism of Apo CII (Apo CIII 유전자 다형성에 따라 영양치료 및 약물 병용치료가 고지혈증 환자의 혈중 지질 농도에 미치는 영향)

  • 조여원;임정은;김수정;김영설
    • Journal of Nutrition and Health
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    • v.33 no.8
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    • pp.813-823
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    • 2000
  • The purpose of this study was to investigate the effects of the nutrition therapy and drug(simvastatin) treatment on the levels of blood lipids for the hyperlipidemic patients according to genetic polymorphism of apo CIII. Subjects of the study consisted of 43(male: 9, female: 34 )hyperlipidemic patients registered to Kyung Hee Medical Center, Intakes of nutrients for the subjects were determined by 24-hr recall method through a personal interviews. The subjects were instructed to take the hypolipidemic and hypocholesterolemic diets. Compliance was monitored through food records, personal interview, and body-weight measurements. The patients changed their basal diet containing 40. 1g fat(182.7mg cholesterol./day) to a diet containing 30.7g fat(139.2mg cholesterol/day) after 12 weeks of nutrition therapy. The distribution of genotypes for apo CIII by Msp I was 32.5% of TT, 50.0% of TC, and 17.5% of CC. aT the beginning of the study, the level of blood triglyceride was the highest for patients with TT and TC. Following the nutrition therapy, patients with CC exhibited the largest drop of blood triglyceride. Following simvastatin treatment with nutrition therapy, blood LDL-cholesterol decreased in most of the patiens with TT. Meanwhile the distribution of genotypes for apo CII by the Fok I was 10.0% of TT, 47.5% of TC, and 42.5% of CC. The level of blood triglyceride was the highest for patients with CC. Following the nutrition therapy, patients with TC exhibited a significant drop for the blood triglyceride. Following simvastatin treatment with nutrition therapy the level of blood LDL-cholesterol decreased in most of the patients with CC. We concluded that dietary habits and food have been changed by nutrition therapy. And blood lipid levels have been decreased by the restriction of intakes of energy, fat and cholesterol. There was variation in the levels of blood lipids according to apo CII polymorphisms. The level of blood lipids responded to nutrition therapy and drug treatment in different was according to genetic polymorphisms. Accordingly, the choice of individualized therapy based on the patient\\`s genetic polymorphism is very important for effective therapy(Korean J Nutrition 33(8) : 813-823, 2000)

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A Study on the Factors which Influenced the Faithfulness to Treatment Among the Pulmonary Tuberculosis Patients Registered in a City Health Center (시보건소 결핵등록관리환자들의 치료충실도에 미치는 요인에 관한 조사 -서울특별시 일개 구보건소 등록환자 중심-)

  • Lee, Young-Woo
    • Journal of Preventive Medicine and Public Health
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    • v.17 no.1
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    • pp.127-135
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    • 1984
  • Personal and social characteristics, disease status, reason of delay of receiving drug from City Health Center and knowledge and attitude on the pulmonary tuberculosis were compared between the faithful group in treatment and the unfaithful group among the patients for pulmonary tuberculosis registered in a City Health Center in order to analyze the factors which influenced the faithfulness to treatment. Record as well as interview survey was done toward all patients of 247 who were registered and being cared during over 6 months in a City Health Center from April 1, 1982 to March 31, 1983, and results were as follows; 1. There was no statistically significant difference in sex and age distribution between the faithful group in treatment and the unfaithful group. 2. There was no statistically significant difference in marital status distribution between the faithful group and unfaithful group in treatment. 3. The lower education group comprised higher proportion than the higher education group among the faithful group in treatment. 4. The proportion of the emlployed was higher than unemlpoyed among the unfaithful group in treatment. 5. The proportion of mild case was higher than severe case among the unfaithful group in treatment. 6. As for the onset of delay of receiving drug, 'less than 3 month after starting treatment' was 59.5% among the unfaithful group in treatment. 7. The reasons of delay of receiving drug were 'no time' (42.2%). 'being away from home' (25.0%), 'being sick' (13.8%), and 'forgot the appointed date' (12.0%). 8. There was no statistically significant difference in the knowledge on the communicability of the tuberculosis between the faithful groups in treatment and the unfaithful group. 9. There was no statistically significant difference in the knowlege on B.C.G. as vaccination drug of tuberculosis between the faithful group and the unfaithful group in treatment. 10. There was no statistically significant difference in the satisfaction on the treatment of health center between the group of faithful and unfaithful in treatment. 11. There was no statistically significant difference in the belief on the complete recovery of tuberculosis between the faithful group and the unfaithful group in treatment. 12. The rate of consulting on tuberculosis treatment with life partner was higher among the faithful group in treatment than the unfaithful group.

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Clinical Observations of the Drug Induced Hepatitis during Antituberculosis Medication (항결핵제 투여 중 나타난 간기능 장애의 임상적 고찰)

  • Park, Moon-Hwan;Yun, Sang-Won;Kim, Kung-Ho;Lee, Mung-Sun;Cho, Dong-Ill;Rhu, Nam-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.405-412
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    • 1994
  • Background: In Korea, the prevalence of tuberculosis and hepatitis is high, and combined therapy with rifampicin and pyrazinamide is used in tuberculosis, so drug induced hepatitis is not only problem of tuberculosis therapy but also cause of treatment failure. However most of recent reports on drug induced hepatitis during antituberculosis medication have dealt with its pathogenesis and have stressed the biochemical, and histopathological aspects of the disorder, whereas this study was designed primarily to provide information on the clinical features. Method: The subjects of study were 1414 patients treated with antituberculosis drugs on the department of chest medicine at National Medical Center during the 5-year 6-month period from January 1, 1988, to June 30, 1993. Retrospective analysis of clinical features for the 29 patients who developed drug induced hepatitis was done. Results: 1) The incidence of antituberculosis drug induced hepatitis was 2.1%. 2) Male to fema1e ratio of antituberculosis drug induced hepatitis was 2:1, but case rates among males and females were not significantly different. 3) Rates of drug induced hepatitis according to age distribution shows the most common incidence between 35 to 49 year old age group, but rates among groups of age were not significant1y different. 4) Drug induced hepatitis was most common in the case of moderate advanced pulmonary tuberculosis(rate is 2.78%), but rates among types of tuberculosis were not significant1y different. 5) 18 cases(62%) of antituberculosis drug induced hepatitis patients had no signs or symptoms. In remaining cases, they were nausea, vomiting, jaundice, hepatomegaly, icteric sclera, right upper quadrant tenderness in order. 6) 22 cases(76%) of antituberculosis drug induced hepatitis cases had occured within the first month. 7) The duration of abnormal liver function was $28{\pm}5$(Mean${\pm}$SD), ranged from 5 days to 180 days. 8) One case of antituberculosis drug induced hepatitis died. 9) The levels of abnormal GOT ranged from 64 to 1055U/L and GPT from 68 to 931U/L. Conclusion: There are no dicided predisposing factors of antituberculosis drug induced hepatitis, so it should be done biochemical monitoring as well as close monitoring for overt signs or symptoms of hepatitis to avoid the development of irreversible hepatic reaction, especially at the treatment of the first month.

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Prevalence of Bacillus cereus Group in Rice and Distribution of Enterotoxin Genes

  • Jang, Ji-Hyun;Lee, No-A;Woo, Gun-Jo;Park, Jong-Hyun
    • Food Science and Biotechnology
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    • v.15 no.2
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    • pp.232-237
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    • 2006
  • Bacillus cereus group comprising B. cereus, B. thuringiensis, and B. mycoides was differentiated by polymerase chain reaction (PCR) and colony morphology. Prevalence of B. cereus group in rice and distribution of enterotoxin genes were determined as possible food poisoning agents. PCR using primers targeted for gyrB and cry genes could distinguish B. thuringiensis from B. cereus, and B. mycoides was differentiated by rhizoid morphological characteristics on nutrient agar. Among 136 rice and their processed products, prevalence of B. cereus group was 40%. B. cereus group consisted of 54 B. cereus, 11 B. thuringiensis, and 1 B. mycoides. Major isolates were B. cereus, with B. thuringiensis detected up to 10% among edible rice tested. Five enterotoxin genes, hbl, nhe, bceT, entFM, and cytK, were broadly distributed among B. cereus group, especially in B. cereus and B. thuringiensis. Prevalence of B. cereus group in rice and enterotoxin distribution suggest B. thuringiensis and B. cereus are toxigenic strain that should be controlled in rice and its products.

Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin

  • Suh, Dong-Churl;Kim, Yeongseok;Kim, Hyeongmin;Ro, Jieun;Cho, Seong-Wan;Yun, Gyiae;Choi, Sung-Up;Lee, Jaehwi
    • Biomolecules & Therapeutics
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    • v.22 no.1
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    • pp.73-77
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    • 2014
  • The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.

Body Distribution of $^{125}I-rhEGF$ Across Normal and Damaged Rat Skins (정상 및 손상된 흰쥐 피부에 국소 적용된 $^{125}I-rhEGF$의 체내 이행)

  • Lee, Jeong-Uk;Chung, Suk-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • YAKHAK HOEJI
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    • v.41 no.6
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    • pp.730-736
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    • 1997
  • Distribution of radioactivity in the skin tissues, subcutaneous tissues, blood and body organs was examined following topical application of $^{125}I-rhEGF$(0.4 ${\mu}Ci$), in the form of a Pluronic F-127 gel, on the normal and damaged (burned and stripped) skins of SD male rats. The radioactivity in the skin tissues and subcutaneous tissues was 3-5 times higher for the damaged skins than for the normal skin. But pretreatment of the skin with rhEGF (1${\mu}g$)) twice at 24 hr dose intervals affected the distribution of the radioactivity yielding the order of burned skin> stripped skin=normal skin. The decrease for the stripped skin by the pretreatment might be related either to the pathophysiological change of the skin or to the down regulation of the EGF receptor. Liver showed the highest radioactivity in amount following single and multiple administration of the drug to the normal and damaged skins. But,in concentration, the kidney and stomach showed higher value than the liver which is consistent with that kidney is a major eliminating organ of EGF and that EGF exerts its pharmacological effect specifically for the stomach.

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A Bayesian Approach to Assessing Population Bioequivalence in a 2 ${\times}$ 2 Crossover Design

  • Oh, Hyun-Sook;Ko, Seoung-Gon
    • Proceedings of the Korean Statistical Society Conference
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    • 2002.05a
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    • pp.67-72
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    • 2002
  • A Bayesian testing procedure is proposed for assessment of bioequivalence in both mean and variance which ensures population bioequivalence under normality assumption. We derive the joint posterior distribution of the means and variances in a standard 2 ${\times}$ 2 crossover experimental design and propose a Bayesian testing procedure for bioequivalence based on a Markov chain Monte Carlo methods. The proposed method is applied to a real data set.

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