• 한국임상약학회지
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• 제32권3호
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• pp.185-190
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• 2022

Background: Denosumab (Prolia®) is administered every 6 months for osteoporosis treatment. Co-administration of calcium and vitamin D is required to minimize hypocalcemia risk. We evaluated clinical outcomes based on the administration interval of denosumab and co-prescription with calcium-vitamin D combination products. Methods: A retrospective study was conducted using electronic medical records from 668 patients who started denosumab therapy between January 1 and December 31, 2018, at Seoul National University Bundang Hospital. Clinical outcomes, as measured by changes in T-score, were evaluated by the intervals and concurrent prescriptions with calcium-vitamin D combination products. Results: Of the 668 patients, 333 patients met the eligibility criteria. These patients were divided into two groups based on appropriateness of the administration interval: "Appropriate" (304 patients, 91.3%) and "Inappropriate" (29 patients, 8.3%). T-score changes were significantly higher in the "Appropriate" than in the "Inappropriate" group (0.30±0.44 vs. 0.13±0.37, p=0.048). At the beginning of the treatment, 221 patients (66.4%) were prescribed calcium-vitamin D combination products, but the changes in T-scores were not significantly different by the prescription status of the product (0.29±0.46 vs. 0.28±0.38, p=0.919). Conclusion: T-scores were significantly improved in patients with appropriate administration intervals. No significant changes in T-scores were observed by the prescription status with calcium-vitamin D combination products. For optimal treatment outcomes, prescribers should encourage adherence to the approved prescription information on dosage and administration, and pharmacists should provide medication counseling for patients.

• 한국근적외분광분석학회:학술대회논문집
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• 한국근적외분광분석학회 2001년도 NIR-2001
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• pp.3112-3112
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• 2001

Near-Infrared Spectroscopy (NIRS) was investigated aiming at the identification of falsified drugs. The identification is based on comparison of the NIR spectrum of a sample with a typical spectra of an authentic drug using multivariate modelling and classification algorithms (PCA/SIMCA). Two spectrophotometers (Brimrose - Luminar 2000 and 2030), based on acoustic-optical filter (AOTF) technology, sharing the same controlling computer, software (Brimrose - Snap 2.03) and the data acquisition electronics, were employed. The Luminar 2000 scans the range 850 1800 nm and was employed for transmitance/absorbance measurements of liquids with a transflectance optical bundle probe with total optical path of 5 mm and a circular area of 0.5 $\textrm{cm}^2$. Model 2030 scans the rage 1100 2400 nm and was employed for reflectance measurement of solids drugs. 300 spectra, acquired in about 20 s, were averaged for each sample. Chemometric treatment of the spectral data, modelling and classification were performed by using the Unscrambler 7.5 software (CAMO Norway). This package provides the Principal Component Analysis (PCA) and SIMCA algorithms, used for modelling and classification, respectively. Initially, NIRS was evaluated for spectrum acquisition of various drugs, selected in order to accomplish the diversity of physico-chemical characteristics found among commercial products. Parameters which could affect the spectra of a given drug (especially if presented as solid tablets) were investigated and the results showed that the first derivative can minimize spectral changes associated with tablet geometry, physical differences in their faces and position in relation to the probe beam. The effect of ambient humidity and temperature were also investigated. The first factor needs to be controlled for model construction because the ambient humidity can cause spectral alterations that should cause the wrong classification of a real drug if the factor is not considered by the model.

• 보건행정학회지
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• 제21권2호
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• pp.249-262
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• 2011

Since May 1st in 2008, the products of ginkgo biloba extract have had to be used with the patient's out-of-pocket payment due to reimbursement restriction guidelines. This study aims to analyze the policy effects of reimbursement restriction on pharmaceutical expenditures using interrupted time series(ITS) analysis. We retrieved monthly NHI claims data for the period between May, 2005 and December 2009. The ingredients identified as a substitute for ginkgo biloba have similar indications based on the similar pharmacological activities. The effects of changes in reimbursement scope were evaluated both for all relevant pharmaceuticals within the same therapeutic class and for 2 separate groups : ginkgo biloba's and its substitutes. According to the study results, restrictions on reimbursement scope resulted in savings of the drug expenditures in the targeted therapeutic class. Direct restriction on ginkgo biloba was associated with a decrease in expenditure level by 60.1% and changes in trend from an average increase rate of 1.4% to an average decrease rate of 1.5% for the therapeutic class, with a dramatic decrease in expenditure level(-191.5%) for ginkgo biloba itself, but with an increased expenditure level(+50.1%) and changes in trend from an average increase rate of 2.0% to an average decrease rate of 1.0% for the substitute group. Further policy to restrict nicergoline was associated with additional decrease in expenditure level for the therapeutic class. Additionally, we could identify the balloon effect - a new policy squeezing one part results in bulging out elsewhere. After the restriction of ginkgo biloba, the utilization of and expenditures on its substitutes increased significantly. In conclusion, we demonstrated that consecutively introduced policies effectively reduced overall expenditures on the therapeutic class of interest. Some ingredients played as a substitute while others did not. Further studies need to be conducted to identify which factors determine a substitute.

• 한국환경농학회지
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• 제25권2호
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• pp.174-179
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• 2006

Chinese cabbage, Braccica campestris has long been consumed as a staple food for Koreans in various forms of fresh, salted, and fermented Kimchi. Cultivation of the crop under greenhouse has become a general practices to fulfill its off-seasonal consumer's demand. However, agricultural practices of the crop have always accompanied with heavy applications of pesticides caused by severe outbreaks of diseases and pose under warm and humid circumferences. Since dissipation patterns of pesticide residues in/on the crop under greenhouse conditions ate quite different from those in the open-air, changes of diazinon, O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphornthioate, in/on the Chinese cabbage applied by foliar spraying under greenhouse were studied. Diazinon 34% EC was applied with dilution of recommended and double dose to the crop. The shoots of crop were harvested immediately after this application and at regular intervals over a 10-day. After sample preparations, the diazinon residue was analyzed using gas chromatography equipped with electron capture detector (GC/ECD). Initially deposited amount of the chemical in/on the crop right after applications with recommended and double doses were 8.3 and 15.2 mg/kg, respectively. The residue levels after 10 days of application were 0.03 and 0.09 mg/kg with 1.3 and 1.5 days of half-life in/on the crop, respectively. In consequent 10 days of pre-harvest interval (PHI) for diazinon EC formulation in/on Chinese cabbage under greenhouse condition was fulfill maximum residue level set by Korea Food and Drug Administration (KFDA, 0.1 mg/kg).

• 한국응용과학기술학회지
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• 제37권6호
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• pp.1528-1534
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• 2020

본 연구는 국내 고령친화산업의 동향을 살펴보고, 고령화 화장품의 식품의약품안전처 고시성분, 고시 외 원료 연구 동향 분석 등을 조사하여 고령친화산업이 화장품 산업 환경과 고령화들의 변화를 빠르게 대처하기 위한 자료를 마련하고자 하였다. 식약처 고시 성분 외에 항 노화 화장품의 원료 개발에 관한 연구동향을 살펴보고, 각각의 원료들의 항 노화 효과를 알아보며, 이를 통해 국, 내외에 등재 학술지에 게재되어진 논문을 중심으로 '고령화', '화장품', '안티에이징', '항 노화' 등의 연구논문을 토대로 자료를 종합하였다. 고령화 산업과 관련한 항 노화 화장품의 발전을 이끌기 위하여 식품의약품안전처에서 고시하고 있는 4종 원료 외에 피부를 강화시켜 노화를 방지하는데 효과가 있는 제품에 대한 연구 활동이 끊임없이 진행되고 있다. 기존의 식품의약품안전처장이 고시하고 있는 기능성 화장품 분야에서 단일 연구가 아닌 복합적으로 항 노화에 대한 연구가 과학적으로 뒷받침 될 수 있도록 다양한 기초 연구 활동이 이루어져야 할 것으로 사료되어 진다.

• Toxicological Research
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• 제6권1호
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• pp.41-49
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• 1990

Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

• 의료법학
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• 제15권2호
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• pp.63-89
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• 2014

In 1976, the Dalkon Shield-intrauterine device injured several thousand women in U.S.A. which caused the changes of medical deivce regulation. The Medical Device Regulation Act or Medical Device Amendments of 1976 (MDA) was introduce. As part of the process of regulating medical devices, the MDA divides medical devices into three categories. The class II, and III devices which have moderate harm or more can use the section 510 (k), premarket notification process if the manufacturer can establish that its device is "substantially equivalent" to a device that was marketed before 1976. In 21 U.S.C. ${\S}$ 360k(a), MDA introduced a provision which expressly preempts competing state laws or regulations. After that, the judicial debates had began over the proper interpretation and application of Section 360(k) In February 2008, the U.S. Supreme Court ruled in Riegel v. Medtronic that manufacturer approved by the Food and Drug Administration (FDA)'s pre-market approval process are preempted from liability, even when the devices have defective design or lack of labeling. But the Supreme Court ruled in Medtronic Inc. v. Lora Lohr that the manufactures which use the section 510 (k) process cannot be preempted and in Bausch v. Stryker Corp. that manufactures which violated the CGMP standard are also liable to the damage of patient at the state courts. In 2009, the Supreme Court ruled in Wyeth v. Levine that patients harmed by prescription drugs can claim damages in state courts. This may cause a double standard between prescription drugs and medical devices. FDA Preemption is the legal theory in the United States that exempts product manufacturers from tort claims regarding Food and Drug Administration approved products. FDA Preemption has been a highly contentious issue. In general, consumer groups are against it while the FDA and pharmaceutical manufacturers are in favor of it. This issues also influences the theory of product liability of U.S.A. Complete immunity preemption is an issue need to be more declared.

• Journal of Preventive Medicine and Public Health
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• 제41권2호
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• pp.74-79
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• 2008

Since the positive listing system for prescription drug reimbursement has been introduced in Korea, the number of pharmacoeconomic evaluation studies has increased. However it is not clear if the quality of pharmacoeconomic evaluation study has improved. Due to the lack of randomized clinical studies in Korean health care setting, Korean economic evaluation studies have typically integrated the local cost data and foreign clinical data. Therefore methodological issues can be raised in regard to data coherence and consistency. But the quality of data was not questiened and the potential bias has not been investigated yet. Even though changes in policy have encouraged the undertaking of pharmacoeconomic evaluations, there is few public-side funding for validation study of cost-effectiveness models and data. Several companies perform economic evaluation studies to be submitted on behalf of their own products, but do not want the study results to be disclosed to the academic community or public. To improve the present conduct of pharmacoeconomic evaluations in Korea, various funding sources need to be developed, and, like other multidisciplinary areas, the experts in different fields of study should collaborate to ensure the validity and credibility of pharmacoeconomic evaluations.

• Natural Product Sciences
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• 제12권4호
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• pp.175-192
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• 2006

Screening for the cytotoxicity from plant origin is the first stage for anti-cancer drug development. A variety of terpenoids with exomethylene, epoxide, allyl, $\alpha,\beta-unsaturated$ carbonyl, acetylenes, and $\alpha-methylene-\gamma-lactone$ induces apoptosis and/or differentiation as well as cytotoxicity through the ROS signal transduction pathways. These are found among monoterpenes, sesquiterpenes, triterpenes, flavonoids, coumarins, diarylheptanoids, and even organosulfuric compounds. The most essential characteristics of natural cytotoxic substances is to possess the strong electrophilicity that is susceptible to nucleophilic biomolecules in the cell. Thiol-reductants and superoxide dismutase can block or delay apoptosis. Thus, ROS and the resulting cellular redox-potential changes can be parts of the signal transduction pathway during apoptosis. Disturbance of the balance of oxireduction by the pigment of natural quinones also caused the induction of the differentiation and apoptosis. Saponins with the cytotoxicity are restricted to their monodesmosides, rather than to bisdesmosides. Those saponins exhibited calcium ion-mediated apoptosis in addition to cytotoxicity whereas they showed also differentiation without extracellular calcium ion. The properties on cytotoxicity, apoptosis, and differentiation were assumed to depend on resultant oxidative stress to the cells. In this review, we describe a spectrum of cytotoxic compounds with various action mechanisms.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.75-82
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• 2011

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and $40^{\circ}C$ was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at $40^{\circ}C$. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at $40^{\circ}C$ was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.