1179 Poster Board I-201 Introduction: Intravenous (iv) busulfan can yield a more consistent dosin... more 1179 Poster Board I-201 Introduction: Intravenous (iv) busulfan can yield a more consistent dosing and pharmacokinetic profile than oral formulation, but there is still inter-patient variability in systemic exposure with iv busulfan. GST gene polymorphisms may explain the variability because busulfan is metabolized in liver through conjugation with GST family. Thus, we investigated the influence of polymorphisms of 3 GST genes, GSTA1, GSTM1, and GSTT1 on the clearance of iv busulfan in adult patients undergoing hematopoietic cell transplantation (HCT). Patients and Methods: We analyzed the PK data from 60 patients, who were included in a randomized trial of 4-times-daily (0.8 mg/kg q 6 h) versus once-daily (3.2 mg/kg once a day) iv busulfan in a conditioning therapy for HCT (Biol Blood Marrow Transplant 2007;13:1095). Limited sampling strategy was used for PK studies, which were performed for the first busulfan dosing using a validated LC with tandem MS. Busulfan plasma clearance (C...
An analytical solution is not a numerical solution, and it can calculate concentrations at any ti... more An analytical solution is not a numerical solution, and it can calculate concentrations at any time point without calculating the intervening time points (if the input function was not changed meanwhile). On the contrary, it is necessary to calculate concentrations of intervening many time points if one has only a numerical solution (in other words, if you use numerical integration). If a drug is administered without previous dosing and not an endogenous substance, the drug concentration at time 0 (initial condition) will be zero. However, if the drug is cleared insufficiently from the previous dose or an endogenous substance, the drug concentrations of each compartment at time 0 (the initial condition) would not be zero. This condition is called non-zero initial condition here. With zero initial values, it is not so difficult to have an analytical solution. And, if the pharmacokinetic model is a one-compartment model, Non-zero initial value problem can be solved without much difficulty using the rule of superposition for the drug amount (or concentration). However, if the pharmacokinetic model is a multi-compartment model and the initial condition is not-zero for all compartments, one can not simply use the rule of superposition for the concentrations because the drug of each compartment moves between compartments. For the simulation, numerical integration is often sufficient. However, for the fitting or estimation, an analytical solution is usually better because of the speed. Solutions with a single dose or zero-initial value are easily found in textbooks. However, solutions for the multi-compartment model with non-zero initial value are harder to find. Authors would like to present the most elegant way to solve this kind of problems analytically. Reviewer This article was invited and reviewed by the peer experts who are not TCP editors.
In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in ... more In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in glucose control via the combined use of agents, but also increase patient compliance. The aim of this study was to assess the pharmacokinetic equivalence of the high dose of the FDC tablet (gemigliptin/metformin sustained release [SR] 50/1,000 mg) and a corresponding co-administered dose of individual tablets. This study was randomized, open-label, single dose, two treatments, two-period, crossover study, which included 24 healthy subjects. Subjects received the FDC or individual tablets of gemigliptin (50 mg) and metformin XR (1,000 mg) in each period. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of maximum plasma concentration (C) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC) of the FDC tablet and co-administration of individual tablet for both gemigliptin and metformin were calculated. The ...
Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzy... more Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty-four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25-mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.
Nurse staffing level is an important factor on nursing sensitive outcome. The relationships of nu... more Nurse staffing level is an important factor on nursing sensitive outcome. The relationships of nurse staffing level with nursing sensitive outcomes such as mortality, upper gastrointestinal bleeding and pressure ulcer have been explored in the United States, Canada, Australia, and New Zealand. Lower level of hospital nurse staffing seems associated with more adverse outcomes, especially mortality. However, there is insufficient evidence of the nurse staffing level-outcome relationship in other indicators. This study was conducted to describe the status and prove the relationships of nurse staffing level with nursing sensitive outcome indicators for adult medical and surgical inpatients in Korea. Patient and hospital characteristics as covariates on nurse sensitive outcome were also explored. This was a retrospective observational study. The study setting was all 46 tertiary hospitals in Korea. We selected all anonymized patients aged 19 years or older and admitted at tertiary hospit...
1179 Poster Board I-201 Introduction: Intravenous (iv) busulfan can yield a more consistent dosin... more 1179 Poster Board I-201 Introduction: Intravenous (iv) busulfan can yield a more consistent dosing and pharmacokinetic profile than oral formulation, but there is still inter-patient variability in systemic exposure with iv busulfan. GST gene polymorphisms may explain the variability because busulfan is metabolized in liver through conjugation with GST family. Thus, we investigated the influence of polymorphisms of 3 GST genes, GSTA1, GSTM1, and GSTT1 on the clearance of iv busulfan in adult patients undergoing hematopoietic cell transplantation (HCT). Patients and Methods: We analyzed the PK data from 60 patients, who were included in a randomized trial of 4-times-daily (0.8 mg/kg q 6 h) versus once-daily (3.2 mg/kg once a day) iv busulfan in a conditioning therapy for HCT (Biol Blood Marrow Transplant 2007;13:1095). Limited sampling strategy was used for PK studies, which were performed for the first busulfan dosing using a validated LC with tandem MS. Busulfan plasma clearance (C...
An analytical solution is not a numerical solution, and it can calculate concentrations at any ti... more An analytical solution is not a numerical solution, and it can calculate concentrations at any time point without calculating the intervening time points (if the input function was not changed meanwhile). On the contrary, it is necessary to calculate concentrations of intervening many time points if one has only a numerical solution (in other words, if you use numerical integration). If a drug is administered without previous dosing and not an endogenous substance, the drug concentration at time 0 (initial condition) will be zero. However, if the drug is cleared insufficiently from the previous dose or an endogenous substance, the drug concentrations of each compartment at time 0 (the initial condition) would not be zero. This condition is called non-zero initial condition here. With zero initial values, it is not so difficult to have an analytical solution. And, if the pharmacokinetic model is a one-compartment model, Non-zero initial value problem can be solved without much difficulty using the rule of superposition for the drug amount (or concentration). However, if the pharmacokinetic model is a multi-compartment model and the initial condition is not-zero for all compartments, one can not simply use the rule of superposition for the concentrations because the drug of each compartment moves between compartments. For the simulation, numerical integration is often sufficient. However, for the fitting or estimation, an analytical solution is usually better because of the speed. Solutions with a single dose or zero-initial value are easily found in textbooks. However, solutions for the multi-compartment model with non-zero initial value are harder to find. Authors would like to present the most elegant way to solve this kind of problems analytically. Reviewer This article was invited and reviewed by the peer experts who are not TCP editors.
In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in ... more In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in glucose control via the combined use of agents, but also increase patient compliance. The aim of this study was to assess the pharmacokinetic equivalence of the high dose of the FDC tablet (gemigliptin/metformin sustained release [SR] 50/1,000 mg) and a corresponding co-administered dose of individual tablets. This study was randomized, open-label, single dose, two treatments, two-period, crossover study, which included 24 healthy subjects. Subjects received the FDC or individual tablets of gemigliptin (50 mg) and metformin XR (1,000 mg) in each period. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of maximum plasma concentration (C) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC) of the FDC tablet and co-administration of individual tablet for both gemigliptin and metformin were calculated. The ...
Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzy... more Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty-four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25-mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.
Nurse staffing level is an important factor on nursing sensitive outcome. The relationships of nu... more Nurse staffing level is an important factor on nursing sensitive outcome. The relationships of nurse staffing level with nursing sensitive outcomes such as mortality, upper gastrointestinal bleeding and pressure ulcer have been explored in the United States, Canada, Australia, and New Zealand. Lower level of hospital nurse staffing seems associated with more adverse outcomes, especially mortality. However, there is insufficient evidence of the nurse staffing level-outcome relationship in other indicators. This study was conducted to describe the status and prove the relationships of nurse staffing level with nursing sensitive outcome indicators for adult medical and surgical inpatients in Korea. Patient and hospital characteristics as covariates on nurse sensitive outcome were also explored. This was a retrospective observational study. The study setting was all 46 tertiary hospitals in Korea. We selected all anonymized patients aged 19 years or older and admitted at tertiary hospit...
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