• 제목/요약/키워드: nonparametric expected maximum (NPEM)

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비모수적 기대최대치(NPEM)연산방법에 의한 미국인과 재미동포 충수돌기염 환자에게 겐타마이신의 모집단 약물동태학 (Population Pharmacokinetics for Gentamicin in American and Korean-American Appendicitis Patients Using Nonparametric Expected Maximum(NPEM) Algorithm)

  • 범진필;최준식
    • 약학회지
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    • 제39권2호
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    • pp.103-112
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    • 1995
  • Population pharmacokinetics for gentamicin were compared with 24 American patients (16 male and 8 female) and 16 Korean-American appendicitis patients(12 male and 4 female). Two to six blood specimens were collected from all patients at the following times: just before a regularly scheduled infusion and at 1/2 hour after the end of a 1/2 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant(K), the slope of the relationship between K versus creatinine clearance(KS), the apparent volume of distribution(V), the slope of the relationship between V versus weight(VS), gentamicin clearance(CL) and the slope of the relationship between CL versus creatinine clearance and the VS(CS). The output includes a 3-dimensional plot of the joint probability density function(PDF), two marginal PDF, means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were 0.424$\pm$0.139(0.00429$\pm$0.00164) and 0.411$\pm$0.135 hr$^{-1}$ (0.00475$\pm$0.00180[hr.mL/min/1.73m$^{2}]^{-1}$) for American and Korean-American populations, respectively. The mean V(VS) were not different at 15.6$\pm$4.77(0.233$\pm$0.0526) and 15.1$\pm$3.84L(0.239$\pm$0.0492 L/kg) for American and Korean-American populations, respectively (P>0.2). The mean CL (CS) were 6.28$\pm$1.85(0.0634$\pm$0.0191) and 5.70$\pm$1.77 L/hr(0.0701$\pm$0.0215 L/kg[hr.mL/min/1.73m$^{2}$)] for American and Korean-American populations, respectively. There are no differences in gentamicin pharmacokinetics between American and Korean-American Appendicitis patients.

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암환자에게 반코마이신의 집단약물동태학 모델연구 (Population Pharmacokinetic Modeling of Vancomycin in Patients with Cancer)

  • 최준식;민영돈;범진필
    • 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.

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위장관 수술환자에서 겐타마이신의 임상약물동태 (Clinical Pharmacokinetics of Gentamicin in Gastrointestinal Surgical Patients)

  • 최준식;문홍섭;최인;범진필
    • 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.

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한국인과 코카시안 충수돌기염 환자에서 비모수적 기대최대치(NPEM) 연산방법에 의한 겐타마이신의 모집단 약물동태학 (Population Pharmacokinetics for Gentamicin in Korean and Caucasian Appendicitis Patients Using Nonparametric Expected Maximum (NPEM) Algorithm)

  • 범진필
    • 한국임상약학회지
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    • 제21권2호
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    • pp.74-80
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    • 2011
  • Population pharmacokinetics for gentamicin were compared with 20 Korean patients (14 male and 6 female) and 25 Caucasian appendicitis patients (16 male and 9 female). Two to six blood specimens were collected from all patients at the following times : just before a regularly scheduled infusion and at 0.5 hour after the end of a 0.5 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant(K), the slope(KS) of the relationship between K versus creatinine clearance(Ccr), the apparent volume of distribution (V), the slope(VS) of the relationship between V versus weight, gentamicin clearance(CL) and the slope(CS) of the relationship between CL versus Ccr and the V. The output includes two marginal probability density function(PDF), means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were$0.402{\pm}0.129hr^{-1}$ ($0.00486{\pm}0.00197[hr{\cdot}mL/min/1.73m^2]^{-1}$) and $0.425{\pm}0.137hr^{-1}$($0.00432{\pm}0.00168[hr{\cdot}mL/min/1.73m^2]^{-1}$) for Korean and Caucasian populations, respectively. The mean V(VS) were not different at $14.3{\pm}3.69L$($0.241{\pm}0.0511L/kg$) and $15.8{\pm}4.81L$($0.236{\pm}0.0531L/kg$) for Korean and Caucasian populations, respectively (P>0.2). The mean CL(CS) were $5.68{\pm}1.69L/hr$ ($0.0714{\pm}0.0222L/kg[hr{\cdot}mL/min/1.73m^2]$) and $6.29{\pm}1.84L/hr$ ($0.0629{\pm}0.0189L/kg[hr{\cdot}mL/min/1.73m^2]$) for Korean and Caucasian populations, respectively. There are no differences in gentamicin pharmacokinetics between Korean and Caucasian appendicitis patients.

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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충수돌기염 환자에서 겐타마이신의 임상약물동태 (Clinical Pharmacokinetics of Gentamicin in Appendicitis Patients)

  • 최준식;정해광;범진필;이진환;김성환
    • 한국임상약학회지
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    • 제5권2호
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    • pp.1-12
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    • 1995
  • The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using linear least square regression(LLSR) and Bayesian analysis in Korean normal volunteers and appendicitis patients. Nonparametric expected maximum(NPEM) algorithm 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 $0.215\pm0.0562,\;0.226\pm0.0325L/kg\;and\;0.339\pm0.0443,\;0.357\pm0.0243hr^{-1}$ for normal volunteers and appendicitis patients using LLSR analysis. Population pharmacokinetic parameters, VS and KS were $0.228\pm0.0614L/kg\;and\;0.00356\pm0.00041(hr{\cdot}mL/min/1.73m^2)^{-1}$ for appendicitis patients using NPEM algorithm. The V and K were $0.232\pm0.0568L/kg\;and\;0.337\pm0.0385hr^{-1}$ for appendicitis patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between LLSR and Bayesian analysis.

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모집단 약물동태학 방법에 의한 겐타마이신 약물동태에 미치는 환경의 영향 (Enviromental Influences on Gentamicin Pharmacokinetics by Using Population Pharmacokinetic Methods)

  • 범진필
    • 약학회지
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    • 제56권1호
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    • pp.48-54
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    • 2012
  • Enviromental differences in gentamicin pharmacokinetics by using population pharmacokinetic methods were compared with 20 Korean patients and 24 Korean-American appendicitis patients. Two to six blood specimens were collected from all patients at the following times : just before a regularly scheduled infusion and at 0.5 hour after the end of a 0.5 hour infusion. Nonparametric expected maximum (NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant (K), the slope (KS) of the relationship between K versus creatinine clearance ($C_{cr}$), the apparent volume of distribution (V), the slope (VS) of the relationship between V versus weight, gentamicin clearance (CL) and the slope (CS) of the relationship between CL versus $C_{cr}$ and the V. The output includes two marginal probability density function (PDF), means, medians, modes, variance and CV%. The mean K (KS) were $0.402{\pm}0.129\;h^{-1}(0.00486{\pm}0.00197\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ and $0.411{\pm}0.135\;h^{-1}(0.00475{\pm}0.00180\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ for Korean and Korean-American populations, respectively. The mean V (VS) were not different at $14.3{\pm}3.6l(0.241{\pm}0.0511l/kg)$ and $15.1{\pm}3.84l(0.239{\pm}0.0492l/kg)$ for Korean and Korean-American populations, respectively (p>0.2). The mean CL (CS) were $5.68{\pm}1.69l/h(0.0714{\pm}0.0222l/kg[h{\cdot}ml/min/1.73\;m^2])$ and $5.70{\pm}1.77l/h(0.0701{\pm}0.0215l/kg[h{\cdot}ml/min/1.73\;m^2])$ for Korean and Korean-American populations, respectively. There were no enviromental differences in gentamicin pharmacokinetics between Korean and Korean-American appendicitis patients.