• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.45-46
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• 2006

• YAKHAK HOEJI
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• v.41 no.2
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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.

• Proceedings of the PSK Conference
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• 2003.04a
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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)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.421.1-421.1
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• 2002

The purposes of this study were to evaluate the population pharmacokinetics of terbinafine according to two-compartment model will, lag time and to investigate the influence of characteristics or subjects such as body weight and age on the pharmacokinetic parameters of terbinatine. Serum data from 73 healthy male Korean subjects were used for this analysis. After overnight fast. each subject received a single 125 mg oral dose of terbinafine. (omitted)

• 대한임상약리학회:학술대회논문집
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• 1995.12a
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• pp.47-47
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• 1995

• 대한임상약리학회:학술대회논문집
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• 1995.12a
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• pp.55-55
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• 1995

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.305.2-306
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• 2001

• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.258-266
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• 2017

Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and to elucidate individual characteristics to affects alcohol's PK or PD including dissolved oxygen. Methods: Following multiple intakes of total 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser (Lion SD-400 $Alcolmeter^{(R)}$). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteen healthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-order absorption and Michaelis-Menten elimination kinetics. $K_a$, V/F, $V_{max}$, $K_m$ is $8.1hr^{-1}$, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced $V_{max}$ (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model of temporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory $E_{max}$ model. $K_{e0}$, $I_{max}$, $E_0$, $IC_{50}$ were $0.23hr^{-1}$, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested that this PK/PD model was robust and has good precision.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• 대한임상약리학회:학술대회논문집
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• 2002.12a
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• pp.7-7
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• 2002