• Title/Summary/Keyword: Two compartment model

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Effects of Temperature on the Pharmacokinetics of Ciprofloxacin in the Cultured Black Rockfish (Sebastes schlegeli) and Olive Flounders (Paralichthys olivaceus)

  • Kim Jin Woo;Jo Mira;Jung Sung Hee;Jee Bo Young;Choi Dong Lim;Jo QTae
    • Fisheries and Aquatic Sciences
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    • v.5 no.3
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    • pp.200-205
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    • 2002
  • Temperature-dependent pharmacokinetics of ciprofloxacin (CIP) was studied in the cultured olive flounders, Paralichthys olivaceus, and black rockfish, Sebastes schlegeli using high performance liquid chromatography (HPLC) originally developed for quinolone determination from livestock. Pharmacokinetics of CIP was apparently affected by ambient water temperature. In a two-compartment model for flounders after oral dosage of 20 mg/kg, $K_{01},\;at\;13^{\circ}C$ and $23^{\circ}C$ were 4.18 and 1.20/hr, respectively. The $K_{10},\;T_{max}\;and\;C_{max}\;at\;13^{\circ}C$ were 5.574/hr, l4.37${\mu}g/mL\;and\;3.15{\mu}g/mL,$ respectively. The corresponding values at $23^{\circ}C$ were l2.84/hr, 15.39${\mu}g/mL\;and\;6.38{\mu}g/mL$, respectively. The AUC, $T_{1/2} (\alpha)\;and\;T_{1/2}\;(\beta)$ were 278.23 ${\mu}g \cdot hr/mL$, 0.24hr and 47.02hr at $13^{\circ}C$ and 3l7.8l${\mu}g \cdot hr/mL$, 0.30 hrs and 60.78hrs at $23^{\circ}C$ for the flounder, respectively. Similar CIP pharmacokinetics were revealed in the black rockfish after oral dosage of 20 mg/kg under the two water temperature regimes. These pharmacokinetical results have some implication in the optimal usage of recently introduced antibacterials in the farmed fish, which were primarily adapted for poultry and mammalian species.

Quantification of myocardial blood low using dynamic N-13 ammonia PET and actor analysis (N-13 암모니아 PET 동적영상과 요소분석을 이용한 심근 혈류량 정량화 방법 개발)

  • Kim, J.Y.;Choi, Y.;Im, K.C.;Choe, Y.S.;Lee, K.H.;Kim, S.E.;Kim, Y.J.;Kim, B.T.
    • Proceedings of the KOSOMBE Conference
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    • v.1997 no.11
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    • pp.575-578
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    • 1997
  • Myocardial blood low (MBF) in human can be noninvasively quantified using dynamic N-13 ammonia PET and two-compartment tracer kinetic model. In this study, factor analysis was used to extract the "pure" blood-pool time-activity curves (TACs) and to generate actor images. ive human N-13 ammonia PET dynamic studies were obtained. Three actors and their corresponding actor images were extracted rom each study. The accuracy of MBF estimated by the actor analysis (FA/FA MBF) was examined by comparing to the values estimated using the conventional ROI method (ROI/ROI MBF). MBF obtained by the actor analysis linearly correlated with MBF obtained by the ROI method (slope=0.98, r=0.91). Input unctions obtained by the two methods agreed well. In conclusion, MBF can be measured accurately and noninvasively with dynamic N-13 ammonia PET imaging and actor analysis. This method is simple and acurate and can measure MBF without blood sampling, ROI drawing nor spillover correction.

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Bioavailability of Ranitidine Tablets in Rats (흰쥐에서 라니티딘제제의 생체이용률)

  • 이미숙;구영순
    • YAKHAK HOEJI
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    • v.39 no.6
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    • pp.636-644
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    • 1995
  • Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

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Predicting of the $^{14}C$ Activity in Rice Plants Exposed to $^{14}CO_2$ Gas for a Short Period of Time ($^{14}CO_2$가스에 단기간 노출된 벼의 $^{14}C$ 오염 예측)

  • Jun, In;Lim, Kwang-Muk;Keum, Dong-Kwon;Choi, Young-Ho;Han, Moon-Hee
    • Journal of Radiation Protection and Research
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    • v.33 no.4
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    • pp.135-141
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    • 2008
  • This paper describes a dynamic compartment model to predict the time-dependent $^{14}C$ activity in a plant as a result of a direct exposure to an amount of $^{14}CO_2$ for a short period of time, and experimental results for the model validation. In the model, the plant consists of two compartments of the body and ears, and five carbon fluxes between the compartments, which are the function of parameters relating to the growth and photosynthesis of a plant, are considered. Model predictions were made for an investigation into the effects of the exposure time, the elapsed exposure time, and the model parameters on the $^{14}C$ radioactivity of a plant. The present model converged to a region where the specific activity model is applicable when the elapsed time of the exposure was extended up to the harvest time of a plant. The $^{14}C$ activity of a plant was predicted to be the greatest when the exposure had happened in the period between the flowering and ears-maturity on account of the most vigorous photosynthesis rate for the period. Comparison of model predictions with the observed 14C radioactivity of rice plants showed that the present model could predict the $^{14}C$ radioactivity of the rice plants reasonably well.

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 Pharmacokinetics of Erythromycin in Cultured Paralichthys olivaceus after Oral administration (경구투여에 의한 양식산 넙치내 Erythromycin의 약물동태학적 특성 분석)

  • Seo, Jung-Soo;Jeon, Eun-Ji;Jung, Sung-Hee;Park, Myung-Ae;Kim, Na-Young
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.2
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    • pp.316-321
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    • 2014
  • The pharmacokinetics of erythromycin (EM) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using LC/MS/MS. After single- or multiple-dose administration of EM (50, 100, 200 mg/kg body weight and 50 mg/kg for 5 days) by oral route in olive flounder ($350{\pm}40g$, $22{\pm}0.5^{\circ}C$), the concentration in the serum was determined at 1, 3, 6, 9, 24, 72, 120, 168, 264, 360, 504 and 720 h post-dose. The kinetic profile of absorption, distribution and elimination of EM in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) following oral administration of 50, 100 and 200 mg/kg b.w. and 50 mg for 5 days. EM was $165.3hr^*{\mu}g/m{\ell}$ ($C_{max}$, $34.63{\mu}g/m{\ell}$; $T_{max}$, 1.56 hr), $212.8hr^*{\mu}g/m{\ell}$ ($C_{max}$, $60.38{\mu}g/m{\ell}$; $T_{max}$, 3.99 hr), and $592.37hr^*{\mu}g/m{\ell}$ ($C_{max}$, $63.01{\mu}g/m{\ell}$; $T_{max}$, 4 hr), respectively. The results of this study related to dosage and ${\mu}{\cdot}$withdrawal times could be used for prescription of EM in field for the treatment of bacterial diseases in olive flounder.

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan;Kang, Wonku
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.648-658
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    • 2017
  • 7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

Preliminary Performance Assessment of a Fuel-Cell Powered Hypersonic Airbreathing Magjet

  • Bernard Parent;Jeung, In-Seuck
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2004.03a
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    • pp.703-712
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    • 2004
  • A variant of the magnetoplasma jet engine (magjet) is here proposed for airbreathing flight in the hypersonic regime. As shown in Figure 1, the engine consists of two distinct ducts: the high-speed duct, in which power is added electromagnetically to the incoming air by a momentum addition device, and the fuel cell duct in which the flow stagnation temperature is reduced by extracting energy through the use of a magnetoplas-madynamic (MPD) generator. The power generated is then used to accelerate the flow exiting the fuel cells with a fraction bypassed to the high-speed duct. The analysis is performed using a quasi one-dimensional model neglecting the Hall and ion slip effects, and fix-ing the fuel cell efficiency to 0.6. Results obtained show that the specific impulse of the magjet is at least equal to and up to 3 times the one of a turbojet, ram-jet, or scramjet in their respective flight Mach number range. Should the air stagnation temperature in the fuel cell compartment not exceed 5 times the incoming air static temperature, the maximal flight Mach number possible would vary between 6.5 and 15 for a magnitude of the ratio between the Joule heating and the work interaction in the MPD generator varied between 0.25 and 0.01, respectively. Increasing the mass flow rate ratio between the high speed and fuel cell ducts from 0.2 to 20 increases the engine efficiency by as much as 3 times in the lower supersonic range, while resulting in a less than 10% increase for a flight Mach number exceeding 8.

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Development of a user-friendly training software for pharmacokinetic concepts and models

  • Han, Seunghoon;Lim, Byounghee;Lee, Hyemi;Bae, Soo Hyun
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.166-171
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    • 2018
  • Although there are many commercially available training software programs for pharmacokinetics, they lack flexibility and convenience. In this study, we develop simulation software to facilitate pharmacokinetics education. General formulas for time courses of drug concentrations after single and multiple dosing were used to build source code that allows users to simulate situations tailored to their learning objectives. A mathematical relationship for a 1-compartment model was implemented in the form of differential equations. The concept of population pharmacokinetics was also taken into consideration for further applications. The source code was written using R. For the convenience of users, two types of software were developed: a web-based simulator and a standalone-type application. The application was built in the JAVA language. We used the JAVA/R Interface library and the 'eval()' method from JAVA for the R/JAVA interface. The final product has an input window that includes fields for parameter values, dosing regimen, and population pharmacokinetics options. When a simulation is performed, the resulting drug concentration time course is shown in the output window. The simulation results are obtained within 1 minute even if the population pharmacokinetics option is selected and many parameters are considered, and the user can therefore quickly learn a variety of situations. Such software is an excellent candidate for development as an open tool intended for wide use in Korea. Pharmacokinetics experts will be able to use this tool to teach various audiences, including undergraduates.

Pharmacokinetics of oxytetracycline in hybrid catfish (Clarias macrocephalus x C. gariepinus) after intravascular and oral administrations

  • Amnart Poapolathep;Kednapat Sriphairoj;Sittichai Hatachote;Kannika Wongpanit;Duangkamol Saensawath;Narumol Klangkaew;Napasorn Phaochoosak;Mario Giorgi;Saranya Poapolathep
    • Journal of Veterinary Science
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    • v.25 no.4
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    • pp.58.1-58.8
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    • 2024
  • Importance: Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). Objective: This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). Methods: In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. Results: The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 ㎍/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). Conclusions and Relevance: These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.