• 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.

• Bulletin of the Korean Chemical Society
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• 제30권11호
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• pp.2631-2636
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• 2009

JHL45, a novel immune modulator for anti-atopic dermatitis and allergic airway disease, was synthesized from decursin isolated from Angelica gigas. In order to conduct a pharmacokinetic study of JHL45, an analytical method, ideally one that uses a minimal amount of biological sample must first be validated. In this study, a HPLC-MS/MS method was developed and validated for the quantification of JHL45 and its major metabolite, (+)-decursinol, from 10 ${\mu}L$ of rat plasma. JHL45 was stable under the analysis conditions, and intra- and inter-day accuracies exceeded 90.06%, with a precision variability ${\leq}$ 13.16% for each analyte. The mean values for Cmax, AUC8h, half-life of JHL45 in rats after intravenous administration of 5 mg/kg JHL45 were 24.59 μg/mL, 10.02 ${\mu}g{\cdot}h/mL$, and 1.88 h, respectively. The validated method herein will be useful for further pharmacokinetic studies of JHL45, as well as in preclinical and clinical phases.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.269-275
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• 2000

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepato-protective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-micro-emulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyma $n^{R}$ 140 soft capsule). In this study, the pharmacokinetic profiles of Silyma $n^{R}$ were examined and compared it with a reference preparation, L Caps140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2$\times$2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The $C_{max}$ and AUC of the Silyma $n^{R}$ were 1542.0 $\pm$ 402.7 ng/ml and 3323.3 $\pm$ 824.7 ng.h/ml, respectively, and were significantly higher than those of reference preparation. The Tmax was 0.8 $\pm$ 0.3 h and significantly shorter than reference preparation. The $K_{e}$ and $T_{1}$2/ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for $C_{max}$, and -61.1% for $T_{max}$./.>././.>./.

• 한국임상약학회지
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• 제22권1호
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• pp.21-29
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• 2012

Modern biologics are biotechnology-derived therapeutics, including recombinant therapeutic proteins like monoclonal antibodies, cytokines and tissue growth factors. Although the pharmacokinetics of therapeutic biologics should be evaluated based on the same general principles as small molecules, careful considerations should be given to bioanalytics and pharmacokinetics when designing pharmacokinetic studies of biologics during their drug development, due to their different physicochemical properties compared with small molecules. The aim of this study was to develop a draft guidance on pharmacokinetic studies of therapeutic biologics in clinical studies. All the elements outlined in the current Food and Drug Administration (FDA), European Medicinal Agency (EMEA), and International Conference on Harmonisation (ICH) guidelines and regulations, and the related literatures previously published were searched and evaluated. In this draft guidance, the specific problems related to the pharmacokinetics of therapeutic biologics that need special consideration during drug development process were addressed, and differences in pharmacokinetic characteristics between biologics and small molecules affecting the content of the development programme were presented.

• 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.

• 한국임상약학회지
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• 제16권1호
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• pp.63-68
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• 2006

Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to ${\gamma}-aminobutyric$ acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced $2{\times}2$ crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. $WinNonlin^{(R)}$, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by $1/(predieted\;y)^2$ was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters $(AUC_{0-24hr},\;AUC_{inf},\;C_{max}\;and\;T_{max})$ and other parameters $(K_a,\;K_{el},\;V_d/F\;and\;Cl/F)$ of $Gapentin^{TM}$ (test drug) and $Neurontin^{TM}$ (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed $AUC_{0-24hr}\;and\;C_{max}$ were $log(0.9106){\sim}log(1.l254)\;and\;log(0.8521){\sim}log(1.0505)$, respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

• 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.

• 약학회지
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• 제42권5호
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• pp.513-518
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• 1998

Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

• 약학회지
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• 제59권2호
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• 분석과학
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• 제34권2호
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• pp.37-45
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• 2021

A rapid and simple LC-MS/MS analytical method in determining Jaspine B has been developed and validated in rat plasma. The standard curve value was 25 - 5000 ng/mL and the linearity, inter-day and intra-day accuracy and precision were within 15.0 % of relative standard deviation (RSD). The mean recoveries of Jaspine B ranged from 87.5 % to 91.2 % with less than 3.70 % RSD and the matrix effects ranged from 91.1 % to 108.2 % with less than 2.6 % RSD. The validated LC-MS/MS analytical method of Jaspine B was successfully applied to investigate the dose-escalated pharmacokinetic study of Jaspine B in rats following an intravenous injection of Jaspine B at a dose range of 1 - 10 mg/kg. The initial plasma concentrations and area under plasma concentration curves showed a good correlation with intravenous Jaspine B dose, indicating the dose independent pharmacokinetics of Jaspine B in rats. In conclusion, this analytical method for Jaspine B can be easily applied in the bioanalysis and pharmacokinetic studies of Jaspine B, including its administration at multiple therapeutic doses, or for making pharmacokinetic comparisons for the oral formulations of Jaspine B in small experimental animals as well as in vivo pharmacokinetic-pharmacodynamic correlation studies.