• 응용통계연구
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• 제34권1호
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• pp.9-23
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• 2021

본 논문에서는 평균장 방법(mean-field methods)을 기반으로 사후 분포(posterior distribution)를 근사하는 방법인 변분 베이즈 방법(variational Bayes methods)에 대해 소개한다. 특히, 모수들을 실수공간으로 변환 후의 결합 사후분포를 가우시안 분포(Gaussian distribution)들의 곱(product)으로 근사하는 방법인 자동 미분 변분 추론(automatic differentiation variational inference)방법에 대해 자세히 소개하고, 환자에게 약물을 투여한 후 시간에 따라 약물의 흐름을 파악하는 연구인 약물동태학 모형(pharmacokinetic models)에 적용한다. 소개된 변분 베이즈 방법을 이용하여 자료분석을 실시하고 마코프 체인 몬테 카를로(Markov chain Monte Carlo)방법을 기초로한 자료분석의 결과와 비교한다. 알고리즘의 구현은 Stan을 이용한다.

• Advances in Traditional Medicine
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• 제8권3호
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• pp.207-214
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• 2008

In recent years, the combined use of Herbal medicines and Western drugs has been increasing. Though certain problems may occur when both types of medicines are taken together, they havenot been adequately analyzed. It was reported that anticoagulation was enhanced in addition tobleeding when patients took long-term warfarin therapy in combination with Salvia miltiorrhiza(danshen), and laxative herbs accelerate intestinal transit and interfere with the absorption. Herbal constituents, curcumin, ginsenosides, piperine, catechins and silymarin were found to beinhibitors of P-glycoprotein. St John's wort induces the intestinal expression of P-glycoprotein. Anthraquinone, quercetin and coumarins were found to be a potent inhibitor of P-450. Glycyrrhizin or liquorice extracts, Garlic and St John's wort are a potent inducer of CYP3A4. This review provides a critical overview of interactions between herbal medicines and other drugs. Hence, it is necessary to study the pharmacodynamic and pharmacokinetic interactions of many herbal medicines between western drugs.

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• 약학회지
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• 제45권6호
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• pp.664-669
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• 2001

Acebutolol is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism through the gastrointestinal tract and liver. The purpose of this study was to report the pharmacokinetic changes of acebutolol (15 mg/kg,oral) and its main metabolite, diacetolol in rabbits pretreated (15 mg/kg, oral) and coadministered (15 mg/kg, S. C., bid for 3 days) with diltiazem. The plasma concentration and area under the plasma concentration-time curves (AUC) of acebutolol and diacetolol were significantly increased in rabbits pretreated and coadministered with diltazem. The elimination rate constant ( $K_{el}$ ) and total body clearances (CL $_{t}$) of acebutolol and diacetolol were significantly decreased and half-life of those were significantly prolonged in the rabbit. Metabolite percentage rate of diacetolol to the plasma concentration of total acebutolol in rabbits pretreated and coadministered with diltiazem were significantly decreased. The results suggest that the dosage of acebutolol should be adjusted when the drug would be administered chronically with diltiazem in a clinical situation.n.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.118-122
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• 2005

The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.

• Mass Spectrometry Letters
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• 제10권1호
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• pp.38-42
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• 2019

Damaurone D belongs to the genus Rosa and is a traditional medicinal product used for the treatment of depression, inflammation, and infectious diseases. The purpose of this study was to develop a simple liquid chromatography-tandem mass spectrometry method for the detection of damaurone D in rat plasma and to demonstrate its application in pharmacokinetic studies. Damaurone D and berberine (internal standard) were extracted with acetonitrile using a protein precipitation method. Mass transition was monitored in multiple reaction monitoring mode at m/z $323.2{\rightarrow}267.0$ for damaurone D and m/z $336.1{\rightarrow}320.0$ for berberine in positive ion mode. Analytical validation was conducted by evaluating the specificity, linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The calibration curves were linear over 2-1000 ng/mL. The intra- and inter-day precision and accuracy of quality control samples were 4.79-13.33% and 86.23-102.75%, respectively. The matrix effect and extraction recovery were 96.11-98.47% and 96.11-102.25%, respectively. In the pharmacokinetic study after intravenous administration of damaurone D at a dose of 3 mg/kg in rats, the area under the curve and clearance of damaurone D in rat plasma were $16750.26{\pm}2676.10min{\cdot}ng/mL$ and $182.44{\pm}31.36mL/min/kg$, respectively.

• 한국임상약학회지
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• 제15권1호
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• pp.34-40
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• 2005

We examined the effects of food on pharmacokinetic and pharmacodynamic properties of fenofibrate released from sustained-release(SR) capsule as therapy for hypolipidemia. Twenty-four healthy volunteers were used in $3{\times}3$ crossover pharmacokinetic and pharmacodynamic study; Additional six volunteers were used as a control group (i.e., no fenofibrate administration). A single dose of fenofibrate (SR capsule, 250 mg) was administered on three occasions: after overnight fasting, after consumption of a standard breakfast, and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high performance liquid chromatography, and pharmacokinetic parameters were calculated using ADAPT II program. Plsama triglyceride concentrations were measured by blood chemistry analyzer (CH-100). The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than did the standard breakfast and fasted conditions. Plasma concentrations of triglyceride at 24 hours decreased significantly after the administration of fenofibrate compared with the concentration at 0 hours(P<0.05). In healthy volunteers, the bioavailability of fenofibrate was greater when administered via sustained-release capsules immediately after the consumption of food than after fasting condition.

• Archives of Pharmacal Research
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• 제28권4호
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• pp.488-492
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• 2005

The purpose of this study is to investigate the bioequivalence of two haloperidol 5 mg tablets, Myung In haloperidol (Myung In Pharm. Co., Ltd., test drug) and $Peridol^{R}$(Whanin Pharm. Co., Ltd., reference drug), and also to estimate the pharmacokinetic parameters of haloperidol in Korean volunteers. The bioavailability and pharmacokinetics of haloperidol tablets were examined on 24 healthy volunteers who received a single oral dose of each preparation in the fasting state in a randomized balanced 2 way crossover design. After an oral dosing, blood samples were collected for a period of 60 h. Plasma concentrations of haloperidol were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with noncompartmental pharmacokinetic analysis. The geometric means of $AUC_{0-60h} and C_{max}$ between test and reference formulations were $17.21\pm8.26 ng\cdot/mL vs 17.31\pm13.24 ng\cdot/mL and 0.87\pm0.74 ng/mL vs 0.85\pm0.62 ng/mL$. respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-60h} and C_{max} were log0.9677{\sim}log1.1201 and log0.8208{\sim}log1.1981$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The geometric means of other pharmacokinetic parameters ($AUC_{inf}. t_{1/2}, V_{d}/F, and CL/F$) between test drug and reference drug were $21.75\pm8.50 ng{\cdot}h/mL vs 21.77\pm15.63 ng{\cdot}h/mL, 29.87\pm8.25 h vs 29.60\pm7.56 h, 11.51\pm5.45 L vs 12.90\pm6.12 L and 0.26\pm0.09 L/h vs 0.31\pm0.17 L/h$, respectively. These observations indicate that the two formulation for haloperidol was bioequivalent and, thus, may be clinically interchangeable.

• 한국임상약학회:학술대회논문집
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• 한국임상약학회 2007년도 추계학술대회
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• pp.192-192
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• 2007

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.223-224
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• 2002

Pharmacokinetic (PK) and pharmacodynamic (PD) study of a new reversible proton pump inhibitor (YH1885, Yuhan Pharmaceutical Co.) was done as a phase 1 clinical trial in Seoul national University Hospital Clinical trialcenter. Single dose of 60, 100, 150, 200, and 300mg were administered to total 20 healthy subjects under fasting state. Six subjects were given 100 mg after food and 12 subjects were given multiple doses of 150 and 300 mg every day for 7 days under fasting state. (omitted)