• Title/Summary/Keyword: Two compartment model

Search Result 115, Processing Time 0.028 seconds

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
    • /
    • v.23 no.2
    • /
    • pp.87-90
    • /
    • 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.

Effects of temperature on pharmacokinetics of oxolinic acid in black rockfish, Sebastes schlegeli following oral administration (조피볼락, Sebastes schlegeli에 경구투여된 oxolinic acid의 약물동태에 미치는 수온의 영향)

  • Jung, Sung-Hee;Kim, Jin-Woo;Seo, Jung-Soo;Jee, Bo-Young;Park, Myoung-Ae
    • Journal of fish pathology
    • /
    • v.23 no.2
    • /
    • pp.221-227
    • /
    • 2010
  • Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of oxolinic acid (OA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of OA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight (average about 500 g). The peak serum concentrations of OA at $23{\pm}1.5^{\circ}C$ and $13{\pm}1.5^{\circ}C$ were $0.60{\mu}/ml$ at 30 h and $2.22{\mu}g/ml$ at 10 h post-dose, respectively. Better absorption of OA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. The elimination of OA from serum was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. Both absorption and elimination of OA were affected significantly by temperature. The kinetic profile of absorption, distribution and elimination of OA in serum was analyzed by fitting to a two compartment model, with WinNonlin program. The AUC, Tmax and Cmax at $23{\pm}1.5^{\circ}C$ were $42.16{\mu}g{\cdot}h/m\ell$, 26.13 h and $0.43{\mu}g/ml$, respectively. The AUC, Tmax and Cmax at $13{\pm}1.5^{\circ}C$ were $131.98{\mu}g{\cdot}h/ml$, 8.81 h and $2.04{\mu}g/ml$, respectively.

Pharmacokinetics of oxytetracycline in rabbits after intravenous and intramuscular administrations (토끼에서 oxytetracycline의 정맥 및 근육 투여시의 약물동태학)

  • Kim, Eun-jung;Yun, Hyo-in;Park, Seung-chun;Oh, Tae-kwang;Cho, Chun-hyung
    • Korean Journal of Veterinary Research
    • /
    • v.34 no.2
    • /
    • pp.259-266
    • /
    • 1994
  • The study was carried out to determine the pharmacokinetic parameters after intravenous(iv) and intramuscular(im) administration (10mg/kr) in healthy rabbits. The results obtained through the experiments were summarized as follows: 1. Bioassay (Bacillus cereus 11778) was evaluated very useful for the determination of oxytetracycline(OTC) in the rabbit serum and tissues, with the detection limit of $0.125{\mu}g/ml$. 2. The pharmacokinetic profiles of OTC (10mg/kg, iv) in rabbits were best described with a two compartment open model $(C=29.5e^{-4,3t}{\pm}3.6^{-0.2t})$, whereas that of OTC (10mg/kg, im) showed a one compartment curve fitting. 3. Following iv administration, a rapid distribution phase was predominant [$t_{\frac{1}{2}}({\alpha}):1.43{\pm}0.98hr$ (♂), $0.5{\pm}0.1hr$(♀)], and then more slow elimination phase ensued [$t_{\frac{1}{2}}({\beta}):4.52{\pm}0.76hr$(♂), $7.32{\pm}2.52hr$(♀)]. Other computer generated pharmacokinetic values were as follows:C1 [$67.76{\pm}18.59ml/kg/h$(♂), $76.03{\pm}22.98ml/kg/h$ (♀)] Vd [$257.74{\pm}180.47ml/kg$ (♂), $92.33{\pm}23.62$ (♀)] AUC [$25.6{\pm}4.44mgh/L$ (♂), $39.6{\pm}12.13mgh/l$ (♀)]. There were no statistical significance between both sexes for all the parameters at the confidence level of 95%. 4. After im administaration, the absorption from the injection sites was very rapid [ Ka:$0.18{\pm}0.03h^{-1}$ (♂), $0.24{\pm}0.02h^{-1}$ (♀)] followed by a monoexponential elimination fashion. The time to peak blood level (Tmax) were calculated $1.64{\pm}0.15hr$ and $1.34{\pm}0.24hr$, in the male and female, respectively. The peak levels (Cmax) at the corresponding time were $1.69{\pm}0.23{\mu}g/ml$ (♂) and $2.08{\pm}0.16{\mu}g/ml$ (♀), with no statistical differences (p>0.05).

  • PDF

Pharmacokinetics of Dehydroevodiamine Following Intravenous Administration in Rats

  • Kim, Seong-Yun;Moon, Chan-Soo;Choi, Yun-Sik;Lee, Sang-Bok
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.8 no.1
    • /
    • pp.65-67
    • /
    • 2004
  • Dehydroevodiamine (DHED) is one of the bioactive components of the Chinese herbal medicine Wu-chu-yu-tang that has been shown to produce various pharmacological effects. In the present study, we investigated the pharmacokinetics of DHED after intravenous administration of two doses (2.5 and 5 mg/kg) in anesthetized rats. The plasma concentration of DHED was measured by reverse-phase high-performance liquid chromatography with UV detection. The mean area under the curve of the time-concentration profile was $21.9\;and\;53.9\;{\mu}g{\cdot}min/ml$ after the 2.5- and 5-mg/kg doses, respectively, and the volume of distribution was 1584.9 and 1580.6 ml following 2.5- and 5-mg/kg doses, respectively. Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. The terminal elimination half-life was $91.8{\pm}16.6\;min$ and $78.7{\pm}11.9\;min$ in the dose of 2.5 and 5 mg/kg, respectively. This is the first report to study the pharmacokinetics of DHED in animals.

Modeling on the Sorption Kinetics of Lead and Cadmium onto Natural Sediments (퇴적물에서의 납과 카드뮴의 흡착 동력학 모델링)

  • Kwak, Mun-Yong;Ko, Seok-Oh;Park, Jae-Woo;Jeong, Yeon-Gu;Shin, Won-Sik
    • Korean Journal of Ecology and Environment
    • /
    • v.39 no.4 s.118
    • /
    • pp.450-461
    • /
    • 2006
  • In this study, sorption kinetics of lead (Pb) and cadmium (Cd) onto coastal sediments were investigated at pH 5.5 using laboratory batch adsorbers. Four different models: one-site mass transfer model (OSMTM), pseudo-first-order kinetic model (PFOKM) ,pseudo-second-order kinetic model (PSOKM) and two compartment first-order kinetic model (TCFOKM) were used to analyze the sorption kinetics. As expected from the number of model parameters involved, the three-parameter TCFOKM was better than the two-parameter OSMTM, PFOKM and PSOKM in describing sorption kinetics of Pb and Cd onto sediments. Most sorption of Pb and Cd was rapidly completed within the first three hours, followed by slow sorption in the subsequent period of sorption. All models predicted that the sorbed amount at the apparent sorption ($q_{e,s}$) equilibria increased as the CEC and surface area of the sediments increased, regardless of initial spiking concentration ($C_0$) and heavy metal and the sediment type. The sorption rate constant ($k_s,\;hr^{-1}$) in OSMTM also increased as the CEC and BET surface area increased. The rate constant of pseudo-first-order sorption ($k_{p1,s},\;hr^{-1}$) in PFOKM were not correlated with sediment characteristics. The results of PSOKM analysis showed that the rate constant of pseudo-second-order sorption ($k_{p2,s},\;g\;mmol^{-1}\;hr^{-1}$) and the initial sorption rate ($v_{o,s},\;mg\;g^{-1}\;hr^{-1}$) were not correlated with sediment characteristics. The fast sorption fraction ($f_{1,s}$) in TCFOKM increased as CEC and BET surface increased regardless of initial aqueous phase concentrations. The sorption rate constant of fast fraction ($k_{1,s}=10^{0.1}-10^{1.0}\;hr^{-1}$) was much greater than that of slow sorption fraction ($k_{2,s}=10^{-2}-10^{-4}\;hr^{-1}$) respectively.

Comparative Bioavailability and Metabolism of Two Capsule Formulations of Fluoxetine in Human Volunteers (플루옥세틴 캅셀제의 지원자에 대한 생체이용율 및 대사율 비교)

  • Kang, Won-Ku;Park, Yong-Soon;Cho, Gyu-Haeng;Choi, Jun-Sik;Kwon, Kwang-Il
    • YAKHAK HOEJI
    • /
    • v.42 no.5
    • /
    • pp.513-518
    • /
    • 1998
  • Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

  • PDF

A Refined Method for Quantification of Myocardial Blood Flow using N-13 Ammonia and Dynamic PET (N-13 암모니아와 양전자방출단층촬영 동적영상을 이용하여 심근혈류량을 정량화하는 새로운 방법 개발에 관한 연구)

  • Kim, Joon-Young;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Ju, Hee-Kyung;Kim, Yong-Jin;Kim, Byung-Tae;Choi, Yong
    • The Korean Journal of Nuclear Medicine
    • /
    • v.31 no.1
    • /
    • pp.73-82
    • /
    • 1997
  • Regional myocardial blood flow (rMBF) can be noninvasively quantified using N-13 ammonia and dynamic positron emission tomography (PET). The quantitative accuracy of the rMBF values, however, is affected by the distortion of myocardial PET images caused by finite PET image resolution and cardiac motion. Although different methods have been developed to correct the distortion typically classified as partial volume effect and spillover, the methods are too complex to employ in a routine clinical environment. We have developed a refined method incorporating a geometric model of the volume representation of a region-of-interest (ROI) into the two-compartment N-13 ammonia model. In the refined model, partial volume effect and spillover are conveniently corrected by an additional parameter in the mathematical model. To examine the accuracy of this approach, studies were performed in 9 coronary artery disease patients. Dynamic transaxial images (16 frames) were acquired with a GE $Advance^{TM}$ PET scanner simultaneous with intravenous injection of 20 mCi N-13 ammonia. rMBF was examined at rest and during pharmacologically (dipyridamole) induced coronary hyperemia. Three sectorial myocardium (septum, anterior wall and lateral wall) and blood pool time-activity curves were generated using dynamic images from manually drawn ROIs. The accuracy of rMBF values estimated by the refined method was examined by comparing to the values estimated using the conventional two-compartment model without partial volume effect correction rMBF values obtained by the refined method linearly correlated with rMBF values obtained by the conventional method (108 myocardial segments, correlation coefficient (r)=0.88). Additionally, underestimated rMBF values by the conventional method due to partial volume effect were corrected by theoretically predicted amount in the refined method (slope(m)=1.57). Spillover fraction estimated by the two methods agreed well (r=1.00, m=0.98). In conclusion, accurate rMBF values can be efficiently quantified by the refined method incorporating myocardium geometric information into the two-compartment model using N-13 ammonia and PET.

  • PDF

Population Pharmacokinetics of Cyclosporine after Hematopoietic Stem Cell Transplantation in Pediatric Patients (조혈모세포 이식을 받은 소아 환자에서 cyclosporine의 집단 약동학 분석)

  • Cho, So Yeon;Kang, Wonku;Yee, Jeong;Kim, Jae Youn;An, Sook Hee;Gwak, Hye Sun
    • Korean Journal of Clinical Pharmacy
    • /
    • v.28 no.1
    • /
    • pp.24-29
    • /
    • 2018
  • Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

Estimation of Tritium Concentration in the Environment based upon Global Tritium Cycling Model (글로벌 삼중수소 순환 모델을 이용한 삼중수소 환경 방사능 추정)

  • Choi, Heui-Joo;Lee, Han-Soo;Kang, Hee-Suk;Lee, Chang-Woo
    • Journal of Radiation Protection and Research
    • /
    • v.28 no.1
    • /
    • pp.1-8
    • /
    • 2003
  • The periodic safety review of operational nuclear power plants requires that the plants should keep a well organized environmental monitoring program. The past records of environment monitoring data were analyzed. and the tritium concentrations of the samples in the surface and ground water around Kori site were measured. It was shown that the tritium concentrations around the Kori site were slightly higher than that of natural background. The change of background tritium concentration was estimated through a numerical modeling. Two different versions of 7 compartments model - the world and the northern hemisphere - defined in NCRP-62 were modeled for the global tritium cycling. The numerical solution of the model was obtained using a computer program, AMBER. The four cases of tritium source-terms into the atmosphere were considered. The results showed that the tritium concentration in the surface soil water was higher than that in sea water or surface stream water. Also, it was shown that the tritium produced by the interaction between cosmic rays and the gases were the major source of tritium, and the tritium produced by nuclear weapon test decreased considerably.

Reduction of Skin Irritation by the Control of Skin Permeation of Methyl Paraben

  • Seong-Hoon Jeong;Mun
    • Journal of the Society of Cosmetic Scientists of Korea
    • /
    • v.23 no.3
    • /
    • pp.108-114
    • /
    • 1997
  • The skin permeation study has two meanings in cosmetics. One is how to promote the skin permeation of active meterials for improving their bioavailabilities and the other is how to decrease it of irritants for reducing their skin side effects. In this study, we selected methyl paraben, one of the preservatives, as a model irritant and tried to reduce the skin irritation by the decrease of skin permeation. Furthermore, the relationship between skin permeation and skin primary irritation was discussed. For in vitro skin permeation experiments, Franz type diffusion cells and the excised skin of female hairless mouse from 8 weeks old were used. The donor compartment was charged with oil only or O/W emulsion containing 0.3% MP. We selected 19 oils, including esters, triglycerides, plant oils, hydrocarbons, and alchols, which are broadly used in cosmetics. We evaluated with female guinea pig. The skin permeahility of MP from the oils showed following order: ester oils > triglycerides > plant oils > hydrocarbons > alcohols. We considered that this result was based on the different effect of each oil on the barrier function of stratum corneum. In O/W emulsion containing each oil, the skin permeability of MP decreased as the oil/water partition coefficient of MP increased. The skin primary irritation increased as the skin permeability of MP increased. In conclusion, we suggest that the skin irritation could be reduced by the decrease of skin permeability of MP, which may be obtained by the good selection of oils in cosmetic preparations.

  • PDF