• Title/Summary/Keyword: Compartment Model

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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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The Heterogeneity of Flow Distribution and Partition Coefficient in [15O-H2O] Myocardium Positron Emission Tomography ([15O-H2O] 심근 양전자 단층 촬영에서 혈류 분포의 비균일성과 분배계수)

  • Ahn, Ji Young;Lee, Dong Soo;Kim, Kyung Min;Jeong, Jae Min;Chung, June-Key;Shin, Seung-Ae;Lee, Myung Chul;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.1
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    • pp.32-49
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    • 1998
  • For estimation of regional myocardial blood flow with O-15 water PET, a few modifications considering partial volume effect based on single compartment model have been proposed. In this study, we attempted to quantify the degree of heterogeneity and to show the effect of tissue flow heterogeneity on partition coefficient(${\lambda}$) and to find the relation between perfusable tissue index(PTI) and ${\lambda}$ by computer simulation using two modified models. We simulated tissue curves for the regions with homogeneous and heterogeneous blood flow over a various flow range(0.2-4.0ml/g/min). Simulated heterogeneous tissue composed of 4 subregions of the same or different size of block which have different homogeneous flow and different degree of slope of distribution of blood flow. We measured the index representing heterogeneity of distribution of blood flow for each heterogeneous tissue by the constitution heterogeneity(CH). For model I, we assumed that tissue recovery coefficient ($F_{MME}$) was the product of partial volume effect($F_{MMF}$) and PTI. Using model I, PTI, flow, and $F_{MM}$ were estimated. For model II, we assumed that partition coefficient was another variable which could represent tissue characteristics of heterogeneity of flow distribution. Using model II, PTI, flow and ${\lambda}$ were estimated. For the simulated tissue with homogeneous flow, both models gave exactly the same estimates, of three parameters. For the simulated tissue with heterogeneous flow distribution, in model I, flow and $F_{MM}$ were correctly estimated as CH was increased moderately. In model II, flow and ${\lambda}$ were decreased curvi-linearly as CH was increased. The degree of underestimation of ${\lambda}$ obtained using model II, was correlated with CH. The degree of underestimation of flow was dependent on the degree of underestimation of ${\lambda}$. PTI was somewhat overestimated and did not change according to CH. We conclude that estimated ${\lambda}$ reflect the degree of tissue heterogeneity of flow distribution. We could use the degree of underestimation of ${\lambda}$ to find the characteristic heterogeneity of tissue flow and use ${\lambda}$ to recover the underestimated flow.

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Effect of gender on the pharmacokinetics and metabolite formation of sulfamethazine in the rabbit (토끼의 성차가 sulfamethazine의 약동학 및 대사산물 생성에 미치는 영향)

  • Yun, Hyo-in;Park, Il-hyun
    • Korean Journal of Veterinary Research
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    • v.32 no.1
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    • pp.35-39
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    • 1992
  • SMZ is one of the most widely used antibacterial agents in veterinary medicine. It is also used as a growth promotant in many species of domestic animals There are marked species differences in its metabolism and pharmacokinetics. However, its pharmacokinetic and metabolism in rabbits. which are ragarded not only as good laboratorty animals hut also as good economical animals in its own, are lacking. Sex-differences in drug metabolism are well recognized in wide range of animal species including rats. Males are known to he more active than females. It is also know that there are Significant differences in the direction of metabolic pathways. But recently, female goats are reported to be more active in the metabolie capacity of SMZ than the other sex by Dutch researchers at Utrecht. Therefore, it is not easy to make general conclusicn of having higher SMZ metal-die capacity in the male compared to the opposite sex in every animal species. In this regard, the study on metabolic pattern of SMZ in rabbits, which are regarded as hervivorous, is of interest because the dietary habbits of rabbit are comparable to thai of goal, NEW Zealand White rabbits of each sex were given SMZ(35mg/kg) as a bolus injection into the marginalean, vein in order to study its pharmacokinetic profiles(using plasma) anc metabolic pattem(24h urine) as specified in the methods anc materials. 1. In the rabbit, the major metabolic pathway of SMZ was the acetylation(the formation of $N_4AcSMZ$). There were hydroxylation pathways(50HSMZ, $6CH_2OHSMZ$) as well, in the metabolism of SMZ in the rabbit, but minor pathways. 2. No sex differences in the metabolic direction of SMZ and its metabolites formation were found from the urinary excreted metabolites of SMZ out of 24h collected urine. 3. The concentration-time curves of SMZ(35mg/kg, iv) in the plasma compartment were fitted to a one-compartment open model when using a computer program(NONLIN). There was also no difference in the pharmacokinetic pattem of SMZ between two sexes. 4. The emergence of $N_4AcSMZ$ metabolized from SMZ was very fast in the plasma of the rabbit The elimination of $N_4AcSMZ$ was prolonged as compared to that of the parent drug Vie found no sex difference in the elimination pattern of $N_4AcSMZ$ in the rabbit.

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Liquid Chromatography Quadrupole Time-Of-Flight Tandem Mass Spectrometry for Selective Determination of Usnic Acid and Application in Pharmacokinetic Study

  • Fang, Minfeng;Wang, Hui;Wu, Yang;Wang, Qilin;Zhao, Xinfeng;Zheng, Xiaohui;Wang, Shixiang;Zhao, Guifang
    • Bulletin of the Korean Chemical Society
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    • v.34 no.6
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    • pp.1684-1688
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    • 2013
  • A rapid and sensitive method for determining usnic acid of Lethariella cladonioides in rat was established using high performance liquid chromatography (HPLC) quadrupole time-of-flight (QTOF) tandem mass (MS/MS). Rat plasma was pretreated by mixture of acetonitrile and chloroform to precipitate plasma proteins. Chromatographic separation was achieved on a column ($50{\times}2.1$ mm, $5{\mu}m$) with a mobile phase consisting of water (containing $5{\times}10^{-3}$ M ammonium formate, pH was adjusted to 3.0 with formic acid) and acetonitrile (20:80, v/v) at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via collision induced dissociation (CID) under negative ionization mode. The MS/MS transitions monitored were m/z 343.0448 ${\rightarrow}$ m/z 313.2017 for usnic acid and m/z 153.1024 ${\rightarrow}$ m/z 136.2136 for protocatechuic acid (internal standard). The linear range was calculated to be 2.0-160.0 ng/mL with a detection limit of 3.0 pg/mL. The inter- and intra-day accuracy and precision were within ${\pm}7.0%$. Pharmacokinetic study showed that the apartment of usnic acid in vivo confirmed to be a two compartment open model. The method was fully valid and will probably be an alternative for pharmacokinetic study of usnic acid.

The Real Fire Test in Bedroom for the Performance Based Fire Design (성능기반 화재안전설계를 위한 침실 공간에서의 실화재 실험)

  • Kim, Hyung-Jun;Kwon, In-Kyu;Kweon, Oh-Sang;Kim, Heung-Youl;Chae, Seung-Un
    • Fire Science and Engineering
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    • v.27 no.6
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    • pp.32-37
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    • 2013
  • For The performance based fire design of the buildings, the fire characteristic such as proceeding and scale of the fire should be figured out but, there is lack of relevant information because of different conditions and difficulties of mock-up test like type of division space, ventilation condition, etc, in buildings. Therefore, in the study, a heal release rate etc, the engineering characteristic data value on the fire is proposed by mock-up fire test for division space in buildings. The mock-up fire test is carried out in a bedroom with 2.4 (L) ${\times}$ 3.6 (W) ${\times}$ 2.4 (H) m model. Initial ignition was started from trash box and the test was carried out for 30 min. As a result of the fire test, flame was broken to outside within 7 min and 50 s after starting the test and the maximum heat release rate was measured as 3,810.6 kW at 9 min and 34 s.

Pharmacokinetic analysis for the development of new potent anti-HIV-1 agents, the KR-V series (새로운 항HIV-1제, KR-V series의 개발을 위한 약물동태연구)

  • Lee, Young-mi;Kim, Jin-suk;Han, Sang-seop;Shin, Ho-chul
    • Korean Journal of Veterinary Research
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    • v.40 no.3
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    • pp.471-478
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    • 2000
  • The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

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Performance Assessment of Low- and Intermediate-Level Radioactive Waste Disposal Facility in Korea by Using Complementary Indicator: Case Study with Radionuclide Flux (보조지표를 활용한 중·저준위 처분시설 성능평가: 방사성 핵종 플럭스 사례연구)

  • Jung, Kang-Il;Jeong, Mi-Seon;Park, Jin Beak
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.13 no.1
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    • pp.73-86
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    • 2015
  • The use of complimentary indicators, other than radiation dose and risk, to assess the safety of radioactive waste disposal has been discussed in a number of publications for providing the reasonable assurance of disposal safety and convincing the public audience. In this study, the radionuclide flux was selected as performance indicator to appraise the performance of engineered barriers and natural barrier in the Wolsong low- and intermediate-level waste disposal facility. Radionuclide flux showing the retention capability by each compartment of the disposal system is independent of assumptions in biosphere model and exposure pathways. The scenario considered as the normal scenario of disposal facility has been divided into intact or degraded silo concrete conditions. In the intact silo concrete, the radionuclide flux has been assessed with respect to the radionuclide retardation performance of each engineered barrier. In the degraded silo concrete, the radionuclide flux has been explored based on the performance degradation of engineered barriers and the relative significance of natural barrier quantitatively. The results can be used to optimally design the near-surface disposal facility being planned as the second project phase. In the future, additional complimentary indicators will be employed for strengthening the safety case for improving the public acceptance of low- and intermediate-level waste disposal facility.

Toxicokinetics of rifapentine in beagle dogs (Beagle dog에 있어서 rifapentine의 독성동태연구)

  • Shin, Ho-chul;Lee, Hye-suk;Cha, Shin-woo;Han, Sang-seop;Roh, Jung-ku;Kim, Jin-suk;Lee, Won-chang
    • Korean Journal of Veterinary Research
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    • v.35 no.4
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    • pp.815-822
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    • 1995
  • The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{\mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{\mu}g{\cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{\mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{\mu}g{\cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{\sim}25.2{\mu}g/ml$, and $10.6{\sim}125.2{\mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively.

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Structural Analysis of Built-in Side-by-Side Refrigerator with Ice Dispenser and Home Bar and Evaluation of Door Differences and Gasket Gap (얼음디스펜서와 홈바가 있는 빌트인 양문형 냉장고의 구조해석 및 도어 단차와 개스킷 간극의 평가)

  • Ryu, Si-Ung;Lee, Boo-Youn
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.9
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    • pp.465-473
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    • 2018
  • A cabinet-door integrated finite element model for a built-in side-by-side refrigerator with an ice dispenser and home bar was constructed, and its deformation was analyzed by ANSYS. As loads, the food load in the shelf and baskets, and thermal load occurring during the normal operation condition were considered. From results of the analyses, the door height difference (DHD) and door flatness difference (DFD) between the two doors, and the increase in the gap of the door gasket, which affects the sealing of cool air in the cabinet, were derived. As results of an evaluation of the differences, the DHD and DFD under the assembled condition satisfied the acceptance criteria of the manufacturer. The food and thermal loads increased the DHD and DFD due to thermal deformation, and the DFD increased significantly. In addition, the increase in the gap of door gasket located between the cabinet and doors was derived from the results of displacements under the food and thermal loads. The evaluation showed that the maximum increase in gap appeared at the left edge of the freezing compartment gasket, which satisfied the acceptance criteria of the manufacturer.

Effects of Temperature on the Uptake and Retention of Cesium-137 by the Clam Cyclina sinensis (가무락조개에 의한 세슘-137 의 농축(濃縮)과 잔류(殘留)에 미치는 온도(溫度)의 영향)

  • Yoo, Byung-Sun;Lee, Jeong-Ho;Lee, Su-Rae
    • Korean Journal of Environmental Agriculture
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    • v.2 no.1
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    • pp.24-29
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    • 1983
  • The effects of temperature on the uptake of $^{137}Cs$ from seawater and on the retention after its uptake by the clam Cycling sinensis was investigated under laboratory conditions. The clams exhibited a greater bioaccumulation of $^{137}Cs$ in $25^{\circ}C$-acclimated animals than those acclimated at $15^{\circ}C$. The viscera of the clams reached the highest bioconcentration factor after 14 days uptake from seawater, but the tissue distribution pattern of $^{137}Cs$ was little influenced, if any, by the uptake temperature. The uptake rate slightly decreased with an increase of temperature in order of $10^{\circ}C$. The radionuclide accumulated in clams was released again in a radionuclide-free seawater according to a two-exponential compartment model. A temperature increase of $10^{\circ}C$ reduced the biological half-life of the long-lived component with a factor of about two, whereas it caused no change in the short-lived component.

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