• Journal of Pharmaceutical Investigation
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• 제39권3호
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• pp.177-183
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• 2009

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of piroxicam in the rabbit plasma. After a treatment of plasma sample by liquid-liquid extraction, the drug was analyzed on an HPLC system with ultraviolet detection at 330 nm. HPLC was carried out using reversed-phase isocratic elution with a C18 column, a mobile phase of a mixture of acetonitril, doubly deionized water and acetic acid 43.74:56.00:0.26 v/v%) at a flow rate of 1.1 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma sample was linear over the concentration range of 0.01-2.0 ${\mu}$g/mL. The intra- and inter-day assay accuracies of this method ranged from 86.82% to 108.33% of normal values and the precision did not exceed 13% of relative standard deviation. The plasma concentration of piroxicam decreased to below the quantifiable limit at 12 hr after the i.v. bolus administration to rabbits following dose of 0.375 mg/kg yielding a apparen t plasma half life of 1.38 hr. The transdermal route prolongs plasma levels of piroxicam. The bioavailability, calculated from the dose-adjusted ratio of the $AUC_{transdermal}$ to the $AUC_{i.v.}$, was 7.44%. The plasma concentration of piroxicam was detected by 48 hr after the transdermal administration of patch at a dose of 32 mg/kg. This method was suitable for cutaneous absorption studies of piroxicam in the rabbit after transdermal administration of different types of dosages of the drug.

• 대한의용생체공학회:의공학회지
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• 제24권1호
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• pp.45-53
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• 2003

Based on the 4-compartmental pharmacokinetic model developed in PART1, target-controlled infusion(TCI) pump system was designed and evaluated. The TCI system consists of digital board including microcontroller and digital signal process(DSP), analog board, motor-driven actuator, user friendly interface, power management and controller. It provides two modes according to the drugs: plasma target concentration and effect target concentration. Anaesthetist controls the depth of anaesthesia for patients by adjusting the required concentration to maintain both plasma and effect site in drug concentration. The data estimated in DSP include infusion rate, initial load dose, and rotation number of motor encoder. During TCI operation, plasma concentration. effect site concentration, awaken concentration, context-sensitive decrement time and system error information are displayed in real time. Li-ion battery guarantees above 2 hours without power line failure. For high reliability of the system, two microprocessors were used to perform independent functions for both pharmacokinetic algorithm and motor control strategy.

• Archives of Pharmacal Research
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• 제29권4호
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• pp.328-332
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• 2006

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

• Journal of Pharmaceutical Investigation
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• 제20권1호
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• pp.29-33
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• 1990

Plasma and saliva concentrations of acetaminophen (AAP) were determined at various time points by HPLC after oral administration of AAP tablets (AAP 500 mg) to four healthy male Korean subjects. Saliva concentrations (S) of AAP were significantly correlated with plasma AAP concentrations (P). The S/P ratio of AAP was calculated to be 1.05 (r =0.944, $p<10^{-6}$) for all the data points from the subjects. It showed a little intersubject variation and ranged from 0.89 to 1.46 in each subject. Bioavailability parameters such as AUC, $C_{max}$ and $T_{max}$ which are usually obtained from the plasma concentration data will be predictable approximately by saliva concentration data. Saliva seems to be very convinient and useful samples for the preliminary studies of bioavailability and bioequivalence of AAP preparations, since it can be collected frequently without any painful venipuncture to the subjects, that is inevitable in plasma sampling. Evaluation of the bioavailability of a preparation by saliva samples will reduce the cost, time and safety risk greatly in developing a new drug delivery system for AAP.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1851-1855
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• 2016

Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

• 대한의용생체공학회:의공학회지
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• 제23권5호
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• pp.341-349
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• 2002

본 논문에서는 혈중 목표 농도 자동 조절기(Target-controlled infusion system. TCI)를 개발하는 것으로써, 마취의가 혈중 목표 농도를 설정하면 사용약제의 약동학적 모델링에 의해서 주입속도를 자동적으로 계산하여 마취의 깊이를 예측하는 약동학적 모델의 수립과 검증 방법을 설명한다. 정확한 약동학적 모델의 구축은 시스템의 성능에 큰 영향을 미치므로 먼저 PART 1에서는 약동학적 모델을 구축하되 3-콤파트먼트 모델과 4-콤파트먼트 모델로 해석하였다. 기존의 TCI에서 사용하고 있는 3-콤파트먼트 모델에 가상의 효과처 구획(Effect Site Compartment)을 만들고 이를 네 버내 구획으로 가정한 4-콤파트먼트 모델(Four-Compartment Model)을 수립하였고, matlab 5.0을 이용하여 비교 분석하였다. 모델은 혈중 목표 농도 주입(Plasma Targeting)과 효과처 목표 농도 주입(Effect Site Targeting), 혈중 농도 유지를 위한 주입율 계산과 기타 마취 상태를 추정하는 정보를 포함한다. 시뮬레이션의 결과를 바탕으로 4-콤파트먼트 모델을 디지털 z-변환을 거쳐 디지털시그널프로세서에 프로그램하고 TCI시스템의 적용가능성을 평가하였다. 정맥 마취용 TCI는 오동작에 대한 검증이 반드시 요구되므로 구축한 모델링에 대한 시뮬레이션의 평가 방법을 설정하였다. 기존의 TCI시스템과는 달리 약동학적 약물 전달 속도 상수(k-파라미터)를 독립적으로 조절할 수 있는 기능이 추가되어 다양한 약제의 사용이 가능할 뿐만 아니라 새로운 약동학적 모델의 개발과 평가에 기여하게 되고, 환자의 체형과 병명에 따른 약동학적 모델의 변화에 대응할 수 있게 하였다.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

• 분석과학
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• 제28권1호
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• pp.17-25
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• 2015

A rapid, sensitive and specific method was developed and validated using electrospray ionization (ESI) tandem mass spectrometry (LC-MS/MS) for determination of misoprostol acid in human plasma. Misoprostol $acid-d_5$ was used as in internal standard (IS). The analyte and IS were extracted by simple one step solid phase extraction (SPE). Linearity in plasma was obtained over the concentration range 10~3000 pg/mL and lower limit of quantification (LLOQ) was identifiable and reproducible at 10 pg/mL. The intra- and inter-day precision values were below 9% and the accuracy was ranged from 93.81% to 102.02% at all four quality control samples. The method was has been successfully applied for routine assay to support pharmacokinetic study of misoprostol acid in human plasma after an oral administration of 0.4 mg misoprostol.

• Journal of Pharmaceutical Investigation
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• 제38권4호
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• pp.277-282
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• 2008

The purpose of the present study was to evaluate the bioequivalence of two topiramate tablets, Topamax tablet (Janssen Korea. Co., Ltd., Seoul, Korea, reference drug) and Topamin tablet (Myungmoon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet at the dose of 100 mg topiramate in a $2{\times}2$ crossover study. There were two-weeks washout period between the doses. Plasma concentrations of topiramate were monitored by an LC-MS/MS for over a period of 96 hr after administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 96 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals of the $AUC_t$, ratio and the $C_{max}$ ratio for Topamin/Topamax were $\log0.88{\sim}\log1.02$ and $\log0.87{\sim}\log1.03$, respectively. These values were within the acceptable bioequivalence intervals of $\log0.80{\sim}\log1.25$. Taken together, our study demonstrated the bioequivalence of Topamax and Topamin with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제37권1호
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• pp.57-62
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two donepezil tablets, $Aricept^{TM}$ tablet (Dae Woong Pharm. Co., Ltd., Korea, reference drug) and $Donpezil^{TM}$ tablet (Dong Wha Pharm. Ind. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing donepezil hydorchloride 10 mg in a $2{\times}2$ crossover study. There was a three-week washout period between the doses. Plasma concentrations of donepezil were monitored by an LC-MS/MS far over a period of 240 hr after the administration. $AUC_t$, (the area under the plasma concentration-time curve from time zero to 240 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$)were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$, No significant sequence effects were found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ and $C_{max}$ were log 0.95${\sim}$log 1.03 and log 0.94${\sim}$log 1.08, respectively. These values were within the acceptable bioequivalence intervals of log 0.80${\sim}$log 1.25. Taken together, our study demonstrated the bioequivalence of $Aricept^{TM}$ and $Donpezil^{TM}$ with respect to the rate and extent of absorption.