• Title/Summary/Keyword: Pharmacokinetic Model

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Preparation and Pharmacokinetic evaluation of Captopril Matrix Tablets with Polyethylene Oxide (폴리에틸렌옥시드를 이용한 캅토프릴 매트릭스 정제의 제조 및 약물동력학적 평가)

  • Jiang, Ge;Baek, Myoung-Ki;Jee, Ung-Kil
    • Journal of Pharmaceutical Investigation
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    • v.29 no.1
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    • pp.7-12
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    • 1999
  • The captopril matrix tablets composed of polyethylene oxide(PEO) was prepared and administered to beagle dogs. Captopril matrix tablets were prepared using direct compressed method and wet granulation compressed method with various ratios of drug to PEO. The diffusion rate of captopril matrix tablets followed on the Higuchi's diffusion model. With increasing hardness of captopril matrix tablets, release rate was decreased. Each formulation was evaluated by the area under the curve (AUC) and time course of plasma captopril concentration after oral administration to beagle dogs. The $AUC_{0-12}$ were $9.126\;{\mu}g\;h/ml$ and $6.417\;{\mu}g\;h/ml$ for the matrix tablets and conventional tablets, respectively. Therefore, the bioavailability of captopril matrix tablets was greater than that of commercial product. It is suggested that captopril matrix tablets using PEO is a useful sustained release formulation.

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Standard Error of Empirical Bayes Estimate in NONMEM$^{(R)}$ VI

  • Kang, Dong-Woo;Bae, Kyun-Seop;Houk, Brett E.;Savic, Radojka M.;Karlsson, Mats O.
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.2
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    • pp.97-106
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    • 2012
  • The pharmacokinetics/pharmacodynamics analysis software NONMEM$^{(R)}$ output provides model parameter estimates and associated standard errors. However, the standard error of empirical Bayes estimates of inter-subject variability is not available. A simple and direct method for estimating standard error of the empirical Bayes estimates of inter-subject variability using the NONMEM$^{(R)}$ VI internal matrix POSTV is developed and applied to several pharmacokinetic models using intensively or sparsely sampled data for demonstration and to evaluate performance. The computed standard error is in general similar to the results from other post-processing methods and the degree of difference, if any, depends on the employed estimation options.

Effect of Drugs on the Cardiac Transport, Metabolism and Action of Idarubicin: Pharmacokinetic and Pharmacodynamic Modeling

  • Kang, Won-Ku
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.212-213
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    • 2002
  • Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity[1]. (omitted)

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Characteristics of Some Animal Models of Experimental Renal Failure (실험적 신장해 모델의 특성 비교)

  • Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.17 no.4
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    • pp.205-211
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    • 1987
  • Renal dysfunction can have pronounced effects on the pharmacokinetic and pharmacodynamic characteristics of drugs. Because the exploration of these effects in patients may be limited by ethical and practical considerations, it often become necessary to perform studies on animals with experimental renal failure(ERF). ERF was produced in rats by the administration of uranyl nitrate, glycerol, salicylate, gentamicin and folate in this study. Changes in glomerular filtration rate(GFR) and renal secretion clearance of tetraethylammonium bromide$(CL^{scn}_{TEA})$, together with morphological changes of kidney cortex were evaluated and compared among ERF models. GFR(or glomeruli) and $CL^{scn}_{TEA}$(or renal tubules) were not damaged parallelly in some ERF model rats. Therefore, it seemed to be necessary to adjust dosage regimen of some basic drugs like TEA in renal dysfunction considering the functional changes of renal secretion in addition to glomerular filtration.

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Recent Methodology in Ginseng Analysis

  • Baek, Seung-Hoon;Bae, Ok-Nam;Park, Jeong-Hill
    • Journal of Ginseng Research
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    • v.36 no.2
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    • pp.119-134
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    • 2012
  • As much as the popularity of ginseng in herbal prescriptions or remedies, ginseng has become the focus of research in many scientific fields. Analytical methodologies for ginseng, referred to as ginseng analysis hereafter, have been developed for bioactive component discovery, phytochemical profiling, quality control, and pharmacokinetic studies. This review summarizes the most recent advances in ginseng analysis in the past half-decade including emerging techniques and analytical trends. Ginseng analysis includes all of the leading analytical tools and serves as a representative model for the analytical research of herbal medicines.

Circadian Changes of Cyclosporine Pharmacokinetics in Rabbits (생체리듬에 따른 싸이클로스포린의 약물동태)

  • Choi, Jon Shik;Park, Bok Soon;Lee, Jin Hwan
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.66-70
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    • 1999
  • The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration $(C_{max})$ of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

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POPULATION PHARMACOKINETICS OF TERBINAFINE IN HEALTHY MALE KOREAN SUBJECTS USING NONMEM

  • Kang, Hyun-Ah;Cho, Hea-Youg;Lee, Suk;Lee, Yong-Bok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.421.1-421.1
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    • 2002
  • The purposes of this study were to evaluate the population pharmacokinetics of terbinafine according to two-compartment model will, lag time and to investigate the influence of characteristics or subjects such as body weight and age on the pharmacokinetic parameters of terbinatine. Serum data from 73 healthy male Korean subjects were used for this analysis. After overnight fast. each subject received a single 125 mg oral dose of terbinafine. (omitted)

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Bioavailability and Comparative Pharmacokinetics of Two Enrofloxacin Formulations in Broiler Chickens (육계에서 경구투여시 enrofloxacin 제제에 따른 생체이용율 및 약물동태)

  • 윤효인;박승춘
    • Journal of Veterinary Clinics
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    • v.14 no.2
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    • pp.195-200
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    • 1997
  • In order to compare the pharmacokinetic profiles of enrofloxacin-HCL)ENFLX-HCL) and enrofloxacin-KOH (ENFLX-KOH) after oral administration in broiler chickens, the study was performed. The chickens used in this study weighed $1.82 {\pm}0.2 kg$ and clinically healthy. The dose of intravenous and lral administration was 5 mg per kg of body weight as enrofloxacin. After intravenous injection of enrofloxacin, it showed two-compartment model with the rapid distribution phase and the slow elimination phase. The mean apparent volume of distribution (Vd) was 2.70 l/kg. The mean half-life of elimination and distribution showed 8.26 h and 0.44 h, respectively. The mean area under curve (AUC) was calculated as $19.7 {\mu} g{\cdot} h/ml$. After oral administration of ENFLX-HCL and ENFLX-KOH with a rate of dose 5 mg of enrofloxacin/kg of body weight, Both of the products were showed one-compartment model unlike that of i.v. enrofloxacin standard solution showed the mean bioavailability of 79.64% for the ENFLX-KOG and 86.24% for the ENFLX-HCL. The mean total body clearance of the former was 0.24 l/kg/h and the latter 0.42 l/kg/h. Both enorfloxacin formulations seemed to have good tissue distribution and penetration as indicated by large volume of distribution : 2.72 l/kg for the -KOH and 4.44 l/kg for the -HCL. With the results obtained in this study, ENFLX-HCL could be used in place of its salt form in chickens.

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Pharmacomkinetics of Roxithromycin after Intravenous Administration in Broilers (록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 분석)

  • Lim Jong-Hwan;Park Byung-Kwon;Kim Myoung-Seok;Hwang Youn-Hwan;Yun Hyo-In
    • Journal of Veterinary Clinics
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    • v.23 no.2
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    • pp.87-90
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    • 2006
  • The aim of the present study was to investigate the disposition pharmacokinetics of roxithromycin in broilers. Roxithromycin was administered at a single dose of 20 mg/kg body weight by intravenous (i.v.) routes. Plasma concentrations of roxithromycin were determined by liquid chromatography/mass spectrometry. After a single i.v. dose plasma concentrations were best fitted to a two-compartment open model. The values of the pharmacokinetic parameters after i.v. administration were: elimination half-life = $5.83{\pm}1.79h$, mean residence time = $6.33{\pm}0.32h$, total body clearance = $0.55{\pm}0.15L/h/kg$, and volume of distribution at steady state = $3.47{\pm}0.84L/kg$. The pharmacokinetic interpretation of roxithromycin after i.v. administration revealed that the drug was well distributed throughout the body in broilers and slowly eliminated. More studies for the application of roxithromycin against poultry disease are needed to establish a suitable pharmaceutical formulation, propose optimum dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

Simulation of lesion-to-liver contrast difference curves in Dynamic Hepatic CT with Pharmacokinetic Compartment Modeling (Pharmacokinetic Compartment Modeling을 이용한 나선식 CT에서의 간암-간 대조 곡선의 Simulation)

  • S.J. Kim;K.H. Lee;J.H. Kim;J.K. Han;B.G. Min
    • Journal of Biomedical Engineering Research
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    • v.20 no.2
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    • pp.173-182
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    • 1999
  • Contrast-enhanced CT has an important role in assessing liver lesions, the optimal protocol to get most effective result is not clear. The mein goal when deciding injention protocol is to optimize lesion detectability with rapid scanning when lesion to liver contrast is maximum. For this purpose, we developed a physiological model of the contrast medium enhancement based on the compartment modeling and pharmacokinetics. Blood supply to liver is achieved in two paths. This dual supply characteristic distinguishes the CT enhancement of liver from that of the other organs. The first path is by hepatic artery and to second, by portal vein. However, it is assumed that only gepatic artery can supply blood to hepatocellular carcinoma(HCC) compartment, thus, the difference of contrast enhancement is resulted between normal liver tissue and hepatic tumor. By solving differential equations for each compartment simultaneously using the computer program Matlab, CT contrast-enhancement curves were simulated. The simulated enhancement curves for aortic, hepatic, portal vein, and HCC compartments were compared with the mean enhancement curves from 24 patients exposed to the same protocols as the simulation. These enhancement curves showed a good agreement. Furthermore, we simulated lesion-to-liver curves for various injection protocols, and the effects were analyzed. The variables to be considered in the injection protocol were injection rate, dose, and concentration of contrast material. These data may help to optimize scanning protocols for better diagnosis.

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