• Title/Summary/Keyword: Crossover study

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Bioequivalence Evaluation of Lovastatin Tablets (로바스타틴 정제의 생물학적 동등성 평가)

  • Bok, Hae Sook;Kim, Myoung Min;Choi, Kyung Eob
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.107-112
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    • 1998
  • Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

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The Influence of Asian Dust, Haze, Mist, and Fog on Hospital Visits for Airway Diseases

  • Park, Jinkyeong;Lim, Myoung Nam;Hong, Yoonki;Kim, Woo Jin
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.4
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    • pp.326-335
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    • 2015
  • Background: Asian dust is known to have harmful effects on the respiratory system. Respiratory conditions are also influenced by environmental conditions regardless of the presence of pollutants. The same pollutant can have different effects on the airway when the air is dry compared with when it is humid. We investigated hospital visits for chronic obstructive pulmonary disease (COPD) and asthma in relation to the environmental conditions. Methods: We conducted a retrospective study using the Korean National Health Insurance Service claims database of patients who visited hospitals in Chuncheon between January 2006 and April 2012. Asian dust, haze, mist, and fog days were determined using reports from the Korea Meteorological Administration. Hospital visits for asthma or COPD on the index days were compared with the comparison days. We used two-way case-crossover techniques with one to two matching. Results: The mean hospital visits for asthma and COPD were $59.37{\pm}34.01$ and $10.04{\pm}6.18$ per day, respectively. Hospital visits for asthma significantly increased at lag0 and lag1 for Asian dust (relative risk [RR], 1.10; 95% confidence interval [CI], 1.01-1.19; p<0.05) and haze (RR, 1.13; 95% CI, 1.06-1.22; p<0.05), but were significantly lower on misty (RR, 0.89; 95% CI, 0.80-0.99; p<0.05) and foggy (RR, 0.89; 95% CI, 0.84-0.93; p<0.05) days than on control days. The hospital visits for COPD also significantly increased on days with Asian dust (RR, 1.29; 95% CI, 1.05-1.59; p<0.05), and were significantly lower at lag4 for foggy days, compared with days without fog (RR, 0.85; 95% CI, 0.75-0.97; p<0.05). Conclusion: Asian dust showed an association with airway diseases and had effects for several days after the exposure. In contrast to Asian dust, mist and fog, which occur in humid air conditions, showed the opposite effects on airway diseases, after adjusting to the pollutants. It would require more research to investigate the effects of various air conditions on airway diseases.

Extraction of Oil from Canola Seeds with Supercritical Carbon Dioxide (초임계 이산화탄소를 이용한 캐놀라 오일 추출)

  • Hwang, Ah-Reum;Jung, In-Il;Lim, Gio-Bin;Ryu, Jong-Hoon
    • KSBB Journal
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    • v.24 no.4
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    • pp.367-376
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    • 2009
  • In this study, two supercritical extraction systems of different scale, analytical-scale and lab-scale, were employed to investigate the extraction efficiency of canola oil from canola seeds using supercritical carbon dioxide ($SCCO_2$) as an extraction solvent. The effects of various parameters such as extraction temperature ($40{\sim}80^{\circ}C$), pressure (200~500 bar), particle size, and $SCCO_2$ flow direction on the extraction rate and yield were examined in detail. Triglycerides and fatty acids in the extracted canola oil were analyzed quantitatively by high-performance liquid chromatography and gas chromatography. The solubility values of canola oil in $SCCO_2$ could be calculated from the experimental results. Similar extraction yields were obtained from both analytical-scale and lab-scale extraction systems. The extraction rates obtained under solvent ($SCCO_2$ ) upflow conditions were found to be higher than those of solvent downflow extraction. However, the effect of $SCCO_2$ flow direction on the extraction yield was observed to be relatively insignificant.

The Influence of Cranial Cervical Ganglion Block in Beagle Dogs with Normal Intraocular Pressure (비글견에서 앞쪽목신경절 차단술이 정상 안압에 미치는 영향)

  • Park, Woo-Dae;Bae, Chun-Sik;Kim, Hwi-Yool
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1472-1476
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    • 2007
  • This study was performed to observe changes of the intraocular pressure following cranial cervical ganglion block with the four different concentrations of lidocaine in beagle dogs with the normal intraocular pressure. We performed by the crossover test in ten beagle dogs divided into four groups, which were 2%, 1%, 0.5% and 0.25% lidocaine group. All experimental dogs received each four times cranial cervical ganglion block using 2 ml of lidocaine with the four different concentrations. The blocks were separately done at a week intervals in random order. Horner#s syndrome was observed in all groups. The intraocular pressure in the blocked side was significantly increased to 5 min in the 1% lidocaine group compared to the baseline (p<0.05). The intraocular pressure of 2% and 1% lidocaine groups were decreased between 25 and 45 min following cranial cervical ganglion block, while those of 0.5% and 0.25% lidocaine groups were unchanged. In conclusion, these results suggest that cranial cervical ganglion block affect on the change of intraocular pressure and 0.5% and 0.25% lidocaine are inadequate concentrations for the change of intraocular pressure in the dog with normal intraocular pressure.

Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene

  • Gopal, Velmani;AL Rashid, Mohammad Harun;Majumder, Sayani;Maiti, Partha Pratim;Mandal, Subhash C
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.7-18
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    • 2015
  • Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4. Methods: The 3D structure of ligands such as hydrogen peroxide ($H_2O_2$), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by $MM^+$ followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of $54{\times}55{\times}56$, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10. Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids. Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

Bioequivalency and Pharmacokinetics of Two Clarithromycin Tablets (Clarithromycin 정제의 생물학적 동등성 및 약물동태)

  • Kang, Won Ku;Park, Sun Young;Park, Yong Soon;Woo, Jong Su;Choi, Kyung Eob;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.49-54
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    • 1999
  • This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

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Bioequivalence and Pharmacokinetics of 70 mg Alendronate Sodium Tablets by Measuring Alendronate in Plasma

  • Yun Min-Hyuk;Woo Jong-Su;Kwon Kwang-Il
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.328-332
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    • 2006
  • The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle

  • Wu, Jinfu;Saovieng, Suchada;Cheng, I-Shiung;Liu, Tiemin;Hong, Shangyu;Lin, Chang-Yu;Su, I-Chen;Huang, Chih-Yang;Kuo, Chia-Hua
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.580-588
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    • 2019
  • Background: Ginsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-${\beta}$-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-${\beta}$-gal in exercising human skeletal muscle. Methods: To examine SA-${\beta}$-gal change, 12 young men (age $21{\pm}0.2years$) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% $VO_{2max}$). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% $VO_{2max}$) was conducted on another 12 participants (age $23{\pm}0.5years$) with the same experimental design. Results: No changes of SA-${\beta}$-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-${\beta}$-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and $CD68^+$ (PLA:+78% vs. Rg1:+121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA:+5% vs. Rg1 -32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01). Conclusion: Rg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.

The Effect of Job Characteristics and Health on Accident Experience according to Age of Transportation Workers (운수업근로자의 연령에 따른 직무특성 및 건강이 사고경험에 미치는 영향)

  • Kwon, Mi-Hwa;Lee, Jae-Shin
    • The Journal of the Korea Contents Association
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    • v.19 no.5
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    • pp.350-362
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    • 2019
  • The purpose of this study was to examine the effects of job characteristics and health on accident experience by analyzing the data of transportation workers according to age. The analysis used data from 'the fourth Korean Working Conditions Survey(KWCS)'. A total of 1,997 transport workers data were finally analyzed, and correlation analysis, crossover analysis and logistic regression analysis were performed. It was confirmed that there was no correlation between the age of the transport workers and the accident experience. In the relationship between the characteristics of transportation workers and the experience of the accident, it was found that, in the case of older workers, there was a significant effect in the order of 'at mistake someone else hurt', 'musculoskeletal problem', 'cardiovascular problem' and 'repetitive movements of hands or arms', the model explaining power was 56.9%(p <.01). In the case of non-older workers, it was found that 'depression and anxiety disorder', 'relationship between job and safety', 'at mistake someone else hurt' and 'labor union', the model explaining power was 21.8%(p <.01). Therefore, in order to promote prevent accidents of transportation workers in future, it is necessary to consider various variables such as health and job characteristics besides age.

Exploratory studies of the music analgesic effect in people with glasses through cold-pressor task (안경 착용 여부에 따른 음악 통증완화효과의 탐색적 연구)

  • Choi, Suvin;Park, Sang-Gue
    • The Korean Journal of Applied Statistics
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    • v.33 no.6
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    • pp.823-832
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    • 2020
  • The analgesic effects of music in people with glasses on perceived pain through cold-pressor task (CPT) is assessed based on three-sequence, three-period, crossover trial with three treatment conditions(music-listening, news-listening, and no-sound) to each subject. Fifty subjects are divided into three sequence groups by randomization, and CPTs under the pre-assigned treatment conditions at each period are performed. Pain responses after each CPT, subjects' pain tolerance (PT) in time scale and pain intensity (PI) and pain unpleasantness (PU) in visual analog scale (VAS) are measured. After classifying the group by whether or not to wear glasses, which is the phenotype of the myopia gene, pain responses are compared by F-tests and Tukey's multiple comparisons. CPT pain responses in group with glasses during the music intervention are significantly different from responses during the news intervention and the control conditions, respectively. This study investigates the pain responses of music intervention in the group wearing glasses, which can be seen as a phenotype of the nearsighted gene, and this result would play a role in explaining the biopsychosocial model of the pain mechanism.