• Title/Summary/Keyword: Safety pharmacology

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Rapid HPLC Method for the Simultaneous Determination of Eight Urinary Metabolites of Toluene, Xylene and Styrene

  • Lee, Cheol-Woo;Lee, Jeong-Mi;Lee, Jae-Hyun;Eom, Han-Young;Kim, Min-Kyung;Suh, Joon-Hyuk;Yeom, Hye-Sun;Kim, Un-Yong;Youm, Jeong-Rok;Han, Sang-Beom
    • Bulletin of the Korean Chemical Society
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    • v.30 no.9
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    • pp.2021-2026
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    • 2009
  • Toluene, xylene and styrene are volatile organic solvents that are commonly used in mixtures in many industries. Because these solvents are metabolized and then excreted in urine, their urinary metabolites are thought to be biomarkers of occupational exposure to these solvents. Therefore, a simple, rapid, and yet reliable analytical method for determining the metabolites is required for accurate biological monitoring. In the present study, a simple and rapid HPLC-UV method was developed for the simultaneous determination of eight major metabolites of toluene, xylene and styrene: hippuric acid (HA), mandelic acid (MA), o-, m- and p-methylhippuric acids (o-, m- and p-MHAs), and o-, m- and p-cresols. A monolithic column was employed as the stationary phase and several conditions, including flow rate, composition of mobile phase and column temperature, were variables for the optimization of the chromatographic resolution. All eight metabolites were successfully resolved within 5 minutes in 10% aqueous ethanol containing 0.3% acetic acid and 1.6% $\beta$-cyclodextrin, using a flow rate gradient of 1.0 - 5.0 mL/min at 25 ${^{\circ}C}$. The performance of this method was validated by linearity, intra- and inter-day accuracy, and precision. The linearity was observed with correlation coefficients of 0.9998 for HA, 0.9999 for MA, 0.9989 for o-MHA, 0.9998 for m-MHA, 0.9991 for p-MHA, 0.9997 for o-cresol, 0.9998 for m-cresol, and 0.9986 for p-cresol. The intra- and inter-day precision of the method were less than 5.89% (CV) and the accuracy ranged from 92.95 to 106.62%. The validity was further confirmed by analysis of reference samples that were prepared by the inter-laboratory quality assurance program of the Korea Occupational Safety and Health Agency (KOSHA, Seoul, Korea). All measured concentrations of the analytes agreed with the certified values.

An Extrapolation from Crop Classifications Based on Pesticide Residues Trial Data within Vegetables in Minor Crops (소면적 재배작물의 농약 잔류성 시험 후 작물 그룹화를 통한 외삽적용)

  • Park, Jong-Hyouk;Mamun, M.I.R.;El-Aty, A.M.Abd;Choi, Jeong-Heui;Im, Geon-Jae;Oh, Chang-Hwan;Shim, Jae-Han
    • The Korean Journal of Pesticide Science
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    • v.13 no.1
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    • pp.28-38
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    • 2009
  • An extrapolation of residue data of seven commonly used pesticides namely bifenthrin, chlorothalonil, cypermethrin, diazinon, fenvalerate, phenthoate and procymidone on a total of 22 minor crops has been carried out in an experimental field trial. The pesticides were applied to 11 leafy-, 5 root- and 6 stem-crops grown in the experimental green-house and the crops and plants were randomly collected at 1, 3, 5, 7 days after application. The average recoveries of applied pesticides were ranged from 72.0 to 117.0% in leafy crops, from 81.3 to 105.0% in stem crops and from 70.1 to 108.1% in the root-crops. Limits of detection (LODs) were 0.005-0.1 mg/kg in the leafy crops and 0.001-0.005 mg/kg in both the stem & root crops. Based on the results of residual dissipation pattern and their morphology, all crops were classified into high and low residual groups. The results showed that it might be possible to extrapolate residual data of stem-crops to root-crops within the same group. Crops that have currently no registered pesticide for use, would be possible to use the pesticides which are already been registered for the similar crops.

Comparative Drug Evaluation of Atorvastatin versus Rosuvastatin in Pharmacotherapy of Korean Patients with Dyslipidemia

  • Park, Seon-Young;Lee, Myung-Koo;Lim, Sung-Cil
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.54-60
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    • 2008
  • Dyslipidemia is the multiple lipid metabolic disorders which is one of the high risk factors for the atherosclerotic diseases. It increases the morbidity and mortality and therefore, must be treated with antilipidemic agents. HMG-Co A reductase inhibitors (statins), one of many antidyslipidemic agents, have shown to be significant improvement from the various cholesterol levels. Especially, data from many comparative trials suggest that rosuvastatin is more effective than atorvastatin among many other statins. The aims of this study were to evaluate the efficacy and safety between rosuvastatin and atorvastatin in the treatment of Korean patients with dyslipidemia. Currently the Korean Society of Lipidology and Atherosclerosis based on the Korean health screening data suggests that Korean patients with dyslipidemia should be treated by the target cholesterol levels according to the Adult Treatment Panel III guidelines of the US National Cholesterol Education Program (NCEP-ATP III). We reviewed retrospectively all medical histories of the total 392 dyslipidemic patients with atorvastatin or rosuvastatin from June 1st, 2004 to August 31st, 2006 in Chungbuk National University Medical Center. Patients were classified as total 4 groups by the NCEP-ATP III Guidelines. The numbers of enrolled patients were each 5 mg atorvastatin (n=34), 10 mg atorvastatin (n=148), 5 mg rosuvastatin (n=94) and 10 mg rosuvastatin (n=82). In comparison between groups, rosuvastatin groups in the lowering LDL-C had better efficacies, and the results were each 22% (5 mg atorvastatin), 33.3% (10 mg atorvastatin), 35% (5 mg rosuvastatin) and 41.3% (10 mg rosuvastatin) with the dose relationship (P=0.000). Rosuvastatin groups also have shown to be more significantly reducing Total Cholesterol levels compared to atorvastatin groups with the no dose relationship (P=0.000). In the lowering of non-HDL cholesteroles, rosuvastatin groups showed significantly better efficacies than atorvastatin with the dose-relationship (P=0.000). Each medication groups did not demonstrate the differences in the changing of HDL cholesterol and triglyceride levels (P=0.096, 0.309, respectively). In conclusion, rosuvastatin was better efficacious than atrovastatin in reducing LDL-C Total Chol, and Tg. Therefore, rosuvastatin is a good antilipidemic agents for Korean patients with dyslipidemia and it can use to minimize the morbidity and mortality related to the cardiovascular diseases in Korean.

Autonomic Nervous Properties of Atropine and Glycopyrrolate on Heart Rate Variability during Anesthesia with Ketamine-Xylazine in Dogs (개에서 케타민-자일라진 마취동안 심박변이도에 대한 아트로핀과 글리코피롤레이트의 자율신경적 특성)

  • Park, Woo-Young;Bae, Chun-Sik;Lee, Soo-Han;Park, Woo-Dae
    • Journal of Veterinary Clinics
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    • v.26 no.3
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    • pp.212-219
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    • 2009
  • Anticholinergics, which are commonly given as a pre-anesthetic medication to prevent adverse effects in canine anesthesia, can cause cardiac adverse effects. To determine the effects of atropine and glycopyrrolate on the balance of sympathetic nervous tone and parasympathetic nervous tone of the heart during ketamine anesthesia in beagle dogs, heart rate variability(HRV), duration of anesthesia and behavioral changes were evaluated. There were no significant temporal domain differences between atropine and glycopyrrolate. Concerning the frequency domain component, atropine and glycopyrrolate effects were significantly lower(P<0.05) than the control saline-treated group. However, the root mean square of the interval differences between consecutive R peaks(RMSSD) and the standard deviation of Poincare plot perpendicular to the line-of-identity(SD1) in atropine were significantly decreased(P<0.05) from the baseline value, and the low frequency/high frequency ratio(LF:HF ratio) in glycopyrrolate was significantly increased from baseline value(P<0.05). The change of SD1 agreed with that of the high frequency(HF) in the frequency domain component and also with those of respiratory rate and $SpO_2-R$. Our results prove that glycopyrrolate is more suitable as a pre-anesthetic anticholinergic in ketamine anesthesia of dogs with respect to safety and duration of action.

Usage and Dosage of Ginseng Radix (panax ginseng C. A. Meyer) Based upon Traditional and Recent Scientific Clinical Applications (인삼의 한의학적 및 현대임상적 측면에서의 복용량 검토)

  • 남기열;박종대
    • Journal of Ginseng Research
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    • v.24 no.2
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    • pp.99-105
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    • 2000
  • Ginsenf Radix (Panax ginseng C. A. Meyer) has been traditionally used as a herbal medicine for many therapeutic or prophylactic purposes in the oriental countries such as Korea, Japan and China for at least two thousand years and also extensively studied in the modern scientific field of chemistry, biochemistry and pharmacology. The herb is now also indicated for use as tonic or a prophylactic and restorative agent for enhancement of mental and physical capacities, in case of weahess exhaustion tiredness loss of concentration, impotence, cold limbs, during illiness anuor convalescence. Ginseng is commonly used in the form of detections, extract and powderl and ginseng products, in the form of capsules tablets and drinks. And also ginseng radix has been widely traditionally prescribed as an important comuonents of manny Chinese prescriptions or alone in various diseases and for health with its different dosages. Nowadays since rinsenf can be generally classified into food or medicine in many nations, it is very difficult to give any exact desnition on the dosage, which may be of particular importance in clinical applications. In addition, the establishment of the reasonable dosage is currently of great significance to meet the demand for such wide applications. Accordingly in this review paper we summarized the dosage of ginseng on the basis of oriental medical books oriental and western pharmacopeias and modern scientific clinical data. The recent survey demonstrated that the averare dosare of finsenf is considered to be three to four grams per day unless prescribed apart, while one to two grams per day in western countries from the western viewpoint of classification of ginseng as a medicine, surrorted by the dosage of not more than one gram per day in most clinical studies. For that reason, it seems likely that the dosage in western countries is ascribed to the safety of ginseng considering side or unwanted effects. Consequently whether the differences of dosage between oriental and western countries depend on dietary habits and races should be closely investigated. Besides, further studies on the pharmacokinetics and bioavailability of ginseng components in clinical trials need to be done to decide optimum dosage of ginseng.

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Bioequivalence Test of Rebamipide 100 mg Tablets (레바미피드 100 mg 정제의 새울학적동등성)

  • Kim, Se-Mi;Cho, Hea-Young;Kang, Hyun-Ah;Lee, Yong-Bok
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.1
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    • pp.38-44
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    • 2008
  • Rebamipide, ($\pm$)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{(R)}$ (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.84$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.

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