• 응용통계연구
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• 제23권3호
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• pp.511-520
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• 2010

약동학 모형은 약동학 모수들의 복잡한 비선형형태의 함수로 복잡한 미분방정식의 형태로 나타나기도 한다. 집단 약동학은 약동학 모형에서 약동학 모수들의 개인 간 차이를 나타내기 위해 이를 랜덤효과로 가정하므로 비선형 혼합 효과 모형이 된다. 본 논문에서는 임상약리학에서 약동학적 특징을 설명하기 위해 사용하는 집단 약동학 모형에 대한 통계학적 고찰을 해 본다. 또한 실제 임상자료를 이용하여 집단 약동학 모형을 적용하여 분석해 봄으로써 통계적 의미를 살펴본다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.84-87
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• 2003

The purposes of this study were to evaluate the population pharmacokinetics of levosulpiride and terbinafine according to several pharmacokinetic models and to investigate the influence of characteristics of subjects such as age, body weight, height and serum creatinine concentration on the pharmacokinetic parameters of levosulpiride and terbinafine, respectively. (omitted)

• 약학회지
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• 제43권2호
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• pp.160-168
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• 1999

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using peak and trough plasma level (PTL) and Bayesian analysis in 20 Korean normal volunteers, 16 gastric cancer and 12 lymphoma patients and also using the compartment model dependent (nonlinear least squares regression: NLSR) and compartment model independent (Lagrange) analysis in 10 ovarian cancer patients. Nonparametric expected maximum (NPEM) algorithm for calculation of the population pharmacokinetic parameters was used, and these parameters were applied for clinical pharmacokinetic parameters by Bayesian analysis. Vancomycin was administered as dose of 1.0 g every 12 hrs for 3 days by IV infusion over 60 minutes in normal volunteers, gastric cancer and lymphoma patients. Population pharmacokinetic parameters, K and Vd in gastric cancer and lymphoma patients using NPEM algorithm were $0.158{\pm}0.014{\;}hr^{-1},{\;}0.630{\pm}0.043{\;}L/kg{\;}and{\;}0.131{\pm}0.0261{\;}hr^{-1},{\;}0.631{\pm}0.089{\;}L/kg$ respectively. The K and Vd in gastric cancer and lymphoma patients using Bayesian analysis were $0.151{\pm}0.027,{\;}0.126{\pm}0.056{\;}hr^{-1}{\;}and{\;}0.62{\pm}0.105,{\;}0.63{\pm}0.095{\;}L/kg$. The K and Vd in ovarian cancer patient using the NLSR and Lagrange analysis were $0.109{\pm}0.008,{\;}0.126{\pm}0.012{\;}hr^{-1}{\;}and{\;} 0.76{\pm}0.08,{\;}0.69{\pm}0.19{\;}L/kg$, respectively. It is necessary for effective dosage regimen of vancomycin in cancer patients to use these population parameters.

• 응용통계연구
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• 제25권1호
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• pp.139-152
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• 2012

집단 약동학 모형 추정의 결과는 환자에게 투약학 약물의 용량결정에 직접적 영향을 미치므로 추정 모형에 대한 타당도와 적합도의 검증이 중요하다. 본 논문에서는 다양한 집단 약동학 모형 적합도 검증을 위한 방법들을 비교, 분석하고 실제 임상자료를 이용하여 최적의 집단 약동학 모형을 찾고 이에 대하여 다양한 타당도, 적합도 검정을 실시하여 모형을 진단해 본다.

• 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.

• 약학회지
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• 제40권1호
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• pp.1-9
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• 1996

The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using nonlinear least square regression(NLSR) and Bayesian analysis in Korean normal volunteers and gastrointestinal surgical patients. Nonparametric expected maximum(NPEM) method for population pharmacokinetic parameters was used. Gentamicin was administered every 8 hours for 3 days by infusion over 30 minutes. The volume of distribution(V) and elimination rate constant(K) of gentamicin were $0.226{\pm}0.032,\;0.231{\pm}0.063L/Kg\;and\;0.357{\pm}0.024,\;0.337{\pm}0.041hr^{-1}$ for normal volunteers and gastrointestinal surgical patients using NLSR analysis. Population pharmacokinetic parameters, KS and VS were $0.00344{\pm}0.00049(hr{\cdot}ml/min/1.73m^2)^{-1}\;and\;0.214{\pm}0.0502L/Kg$ for gastrointestinal surgical patients using NPEM method. The V and K were $0.216{\pm}0.048L/Kg\;and\;0.336{\pm}0.043hr^{-1}$ for gastrointestinal surgical patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between NLSR and Bayesian analysis in gastrointestinal surgical patient.

• 한국임상약학회지
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• 제28권1호
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• pp.24-29
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• 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.

• 약학회지
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• 제46권1호
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• pp.63-68
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• 2002

The purpose of this study was to estimate the population pharmacokinetics of clarithromycin in healthy adult Korean and to investigate the factors influencing the pharmacokinetics of clarithromycin. The population pharmacokinetic parameters of clarithromycin were calculated with the data from healthy adult Koreans. A total of 798 plasma concentrations obtained from 78 subjects after administration of a single oral dose of 250 mg or 500 mg were used for the modeling. The concentration-time data were fitted to a one-compartment open model assuming a first-order absorption and elimination with no lag time. The correlations between various factors [such as sex, age, height, weight, sect creatinine (Scr) and dose and pharmacokinetic parameters were estimated with stepwise linear recession analyses. The selected covariates were incorporated in the population model of NONMEM, and the importance of each covariate was investigated by means of backwards elimination. The apparent clearance (CL/F) was significantly correlated to Scr and sex, and the apparent volume of distribution (Vd/F) was significantly correlated to Scr and height in a nonlinear relationship. The population values of Ka was 1.8 h $r_{-1}$, CL/F was 37.71 L/hr, Vd/F was 200 L and t/ sub 1/2 / was 3.68 hrs for a male Korean with 170 m height and 1.0 mg/dL Scr.

• 약학회지
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• 제57권1호
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• pp.32-36
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• 2013

The purpose of this study was to determine the influence of assay error for improved pharmacokinetic modeling and simulation of vancomycin on the Bayesian and nonlinear least squares regression analysis in 24 Korean gastric cancer patients. Vancomycin 1.0 g was administered intravenously over 1 hr every 12 hr. Three specimens were collected at 72 hr after the first dose from all patients at the following times, at 0.5 hr before regularly scheduled infusion, at 0.5 hr and 2 hr after the end of 1 hr infusion. Serum vancomycin levels were analyzed by fluorescence polarization immunoassay technique with TDX-FLX. The standard deviation (SD) of the assay over its working range had been determined at the serum vancomycin concentrations of 0, 20, 40, 60, 80 and $120{\mu}g/ml$ in quadruplicate. The polynomial equation of vancomycin assay error was found to be SD $({\mu}g/ml)=0.0224+0.0540C+0.00173C^2$ ($R^2=0.935$). There were differences in the influence of weight with vancomycin assay error on pharmacokinetic parameters of vancomycin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynomial equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result suggests the improvement of dosage regimens for the better and safer care of patients receiving vancomycin.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2002년도 춘계심포지움
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• pp.17-17
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• 2002