• 제목/요약/키워드: pharmacokinetic parameter

검색결과 49건 처리시간 0.022초

조피볼락에서 Pefloxacin의 미분쇄가 약물동력학 Parameters에 미치는 영향 (Effects of Pefloxacin Grinding on Pharmacokinetic Parameter in Korean Rockfish)

  • 임영근;양영환;김진우;손상규;심경희;김유정;정한영;최우식;야마모토케이지
    • 생명과학회지
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    • 제9권3호
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    • pp.241-247
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    • 1999
  • Antibiotics have been routinely used to control the disease of farm-raised animals in the aquaculture facilities without any criterion based on a pharmacokinetic study. This lack of information on the effective usage of antibiotics would have brought the farmers to use excessive and/or less dosages, causing the advent of drug-resistant bacteria as well as economic loss and possible contamination of the local farming area. Until recently, few studies on a detailed manual for the antibiotic usage including chemotherapy procedure, dosage, and treatment schedule of the aquatic antibiotics have been conducted throughout the world. To the worse, there is no available criterion for optimal usage of aquatic antibiotics to control diseases in aquatic farms in this country because every country has its own aquacultural system. Therefore, based on the previous studies on the usage of the various antibiotics, our studies are to focus on the development of optimal method for the detection of various antibiotics on the fate of antibiotics applied to the fish, including absorption, circulation, and secretion physiology. Pharmacokinetic study were to sep up the optimal detective condition against residual antibiotics of fish by HPLC. The grinding pefloxacin for 15 min is most effective in dissolution test and pharmacokinetic parameters. Pharmacokinetic parameters were satisfactory for 15 min-grinding products and they can be explained as one-compartment model.

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약물계량학을 이용한 초기임상1상 시험 용량 예측 방법에 대한 비교연구 (Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics)

  • 백인환
    • 한국임상약학회지
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    • 제26권2호
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    • pp.150-162
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    • 2016
  • Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

위암 환자에서 반코마이신의 임상약물동태 (Clinical Pharmacokinetics of Vancomycin in Gastric Cancer Patients)

  • 최준식;장일효;범진필
    • 약학회지
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    • 제41권2호
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    • pp.195-202
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    • 1997
  • The purpose of this study was to determine pharmacokinetic parameters of vancomycin using two point calculation(TPC) and Bayesian methods in 16 Korean normal volunteers and 15 g astric cancer patients. Nonparametric expected maximum(NPEM) algorithm for calculation of population pharmacokinetic parameter was used, and these parameters were applied for clinical pharmacokinetic parameters by Bayesian analysis. Vancomycin was administered 1.0g every 12 hrs for 3 days by IV infusion over 60 minutes. The volume of distribution(Vd), elimination rate constant(Kel) and total body clearance(CLt) of vancomycin in normal volunteers using TPC method were $0.34{\pm}0.06 L/kg,\; 0.19{\pm}0.01 hr^{-1}$ and $4.08 {\pm} 0.93 L/hr$, respectively, The Vd, Kel and CLt of vancomycin in gastric cancer patients using TPC method were $0.46 {\pm} 0.06 L/kg, 0.17{\pm}0.02 hr^{-1}$ and $4.84 {\pm} 0.57 L/hr$ respectively. There were significant differences(p<0.05) in Vd. Kel and CLt between normal volunteers and gastric cancer patients. Polpulation pharmacokinetic parameter, the slope(KS) of the relationship beetween Kel versus creatinine Clearance, and the Vd were $0.00157{\pm}0.00029(hr{\cdot}mL/min/1.73m^2)^{-1},\; 0.631 {\pm} 0.0036 L/kg$ in gastric cancer patients using NPEM algorithm respectively. The Vd and Kel were $0.63{\pm}0.005 L/kg, 0.15 {\pm}0.027 hr^{-1}$ for gastric cancer patients using Bayesian method. There were significant differences(p<0.05) in vancomycin pharmacokinetics between Bayesian and TPC methods. It is considered that the population parameter in the patient population is necessary for effective Bayesian method in clinical pharmacy practise.

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약동학적 파라미터를 이용한 시간경로 마이크로어레이 자료의 군집분석 (Clustering of Time-Course Microarray Data Using Pharmacokinetic Parameter)

  • 이효정;김별아;박미라
    • 응용통계연구
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    • 제24권4호
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    • pp.623-631
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    • 2011
  • 시간경로 마이크로어레이 자료 분석의 주요 목적 중의 하나는 유전자들의 시간에 따른 발현수준의 변화를 고려함으로써 발현패턴에 기초한 유전자들의 그룹을 찾기 위한 것으로, 군집분석을 위한 다양한 알고리즘들이 제안되었다. 본 연구에서 시간경로 마이크로어레이 자료에 대한 군집분석을 위해 두 약물제제 간 생물학적 동등성을 평가하기 위한 약동학 시험에서 사용되는 약동학적 파라미터 값에 기초한 군집분석을 제안하였으며 이를 실제 데이터 및 모의실험 자료에 적용하여 유용성을 검토하였다.

록시스로마이신의 체내동태에 대한 이종간 예측모델 (Interspecies Scaling of Roxithromycin Pharmacokinetics Across Species)

  • 임종환;박병권;윤효인
    • 한국임상수의학회지
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    • 제24권1호
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    • pp.5-9
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    • 2007
  • 본 연구에서는 랫트, 토끼, 닭, 개 등의 각종 동물들의 약물동태학적 파라미터를 이용하여 록시스로마이신의 이종간 예측모델을 수립하였으며, 이때 약물동태학적 파라미터는 반감기, 청소율, 분포용적, 평균체류시간 등을 이용하였다. 이종간 약물동태학적 파라미터의 변화 예측은 체중과 지수적 상관관계 $(Y=aW^b)$를 이용하였으며, 이때 Y는 약물동태학적 파라미터, W는 체중, a는 allometric coefficient를 의미한다. B는 약물동태학적 파라미터와 체중간의 상관관계를 의미하는 비례상수이다. 랫트, 토끼, 닭, 개 등의 약물동태학적 파라미터인 분포용적, 청소율, 반감기, 평균체류시간 등은 체중과 유의한 선형관계를 나타내었다. 본 연구에 의해 수립된 록시스로마이신에 대한 이종간 약물동태학적 파라미터의 이종간 예측모델은 다양한 종의 동물종에 대한 좀 더 정확한 용법용량을 구하는 기초자료로 이용할 수 있을 것이다.

흰쥐에서 라니티딘제제의 생체이용률 (Bioavailability of Ranitidine Tablets in Rats)

  • 이미숙;구영순
    • 약학회지
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    • 제39권6호
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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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정상지원자에서 Cimetidine과 Cyclosporine의 약물상호작용 (Drug Interaction of Cimetidine and Cyclosporine in Human)

  • 최인;최준식
    • 한국임상약학회지
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    • 제7권2호
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    • pp.51-63
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    • 1997
  • The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

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Prognostic Value of Dynamic Contrast-Enhanced MRI-Derived Pharmacokinetic Variables in Glioblastoma Patients: Analysis of Contrast-Enhancing Lesions and Non-Enhancing T2 High-Signal Intensity Lesions

  • Yeonah Kang;Eun Kyoung Hong;Jung Hyo Rhim;Roh-Eul Yoo;Koung Mi Kang;Tae Jin Yun;Ji-Hoon Kim;Chul-Ho Sohn;Sun-Won Park;Seung Hong Choi
    • Korean Journal of Radiology
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    • 제21권6호
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    • pp.707-716
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    • 2020
  • Objective: To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients. Materials and Methods: Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS. Results: The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O6-methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis (p = 0.041, p = 0.032, and p = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL > 0.223 (log-rank p = 0.038 and p = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS (p = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27-134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS. Conclusion: Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.

Optimal Sampling Times of Once Daily Gentamicin in Korean Patients with Urinary Tract Infections

  • Park, Hyo-Jung;Sohn, Kie-Ho;Choi, Kyung-Eob;Shin, Sang-Yup;Jung, Sook-In;Oh, Won-Sup;Peck, Kyong-Ran;Song, Jae-Hoon;Lee, Suk-Hyang
    • Biomolecules & Therapeutics
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    • 제11권3호
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    • pp.178-182
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    • 2003
  • The clinical use of once daily aminoglycoside (ODA) dosing has been increased because of the potential therapeutic advantages of this dosing regimen. To evaluate the optimal sampling times of ODA dosing method in a clinical setting, the study was prospectively conducted in a total of 28 patients with UTI. All of the patients were intravenously administered gentamicin at a dose of 7 mg/kg over 60 minutes and randomly divided into two groups. Blood was collected at 0, 2, and 6 hours in Group A and at 1, 2, and 6 hours in Group B after the end of 1-hour infusion. The pharmacokinetic parameters (Ke, Vd and Cmax) obtained using the 0, 6 hour levels and 2, 6 hour levels in Group A were statistically different while those of 1, 6 hour levels and 2, 6 hour levels in Group B were similar. This finding indicated that the distributional phase of ODA is completed within 1 hour following the end of the I-hour infusion. If we are allowed to collect only two blood samples in ODA considering patients comfort and the analytical cost of drug, the first one should be drawn after 1 hour following the end of infusion to obtain adequate pharmacokinetic information.

Modified Pharmacokinetic/Pharmacodynamic model for electrically activated silver-titanium implant system

  • Tan, Zhuo;Orndorff, Paul E.;Shirwaiker, Rohan A.
    • Biomaterials and Biomechanics in Bioengineering
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    • 제2권3호
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    • pp.127-141
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    • 2015
  • Silver-based systems activated by low intensity direct current continue to be investigated as an alternative antimicrobial for infection prophylaxis and treatment. However there has been limited research on the quantitative characterization of the antimicrobial efficacy of such systems. The objective of this study was to develop a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model providing the quantitative relationship between the critical system parameters and the degree of antimicrobial efficacy. First, time-kill curves were experimentally established for a strain of Staphylococcus aureus in a nutrientrich fluid environment over 48 hours. Based on these curves, a modified PK/PD model was developed with two components: a growing silver-susceptible bacterial population and a depreciating bactericidal process. The test of goodness-of-fit showed that the model was robust and had good predictability ($R^2>0.7$). The model demonstrated that the current intensity was positively correlated to the initial killing rate and the bactericidal fatigue rate of the system while the anode surface area was negatively correlated to the fatigue rate. The model also allowed the determination of the effective range of these two parameters within which the system has significant antimicrobial efficacy. In conclusion, the modified PK/PD model successfully described bacterial growth and killing kinetics when the bacteria were exposed to the electrically activated silver-titanium implant system. This modeling approach as well as the model itself can also potentially contribute to the development of optimal design strategies for other similar antimicrobial systems.