• 약학회지
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• 제46권4호
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• pp.290-294
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• 2002

Cephradine is an orally absorbed cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria and is highly resistant to beta-lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cephradine capules, Cephradine capsule (Donggu Pharmaceutical Co., reference drug) and Cephradine capsule (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration. Twenty-six normal volunteers, 24.6 $\pm$ 3.70 years in age and 62.4 $\pm$ 8.99 kg in body weight, were divided into two groups and a randomized 2 $\times$ 2 cross-over study was employed. After one capsule containing 250 mg of cephrdine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephrdine in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as AU $C_{t}$ to $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt, $C_{max}$ and $T_{max}$ between two products were 2.89％, 1.05％ and 1.06％, respectively, when calculated against the reference drug. The 90％ confidence intervals were within log0.8 $\leq$ $\delta$ $\leq$ log1.25 (e.g., log0.9803 $\leq$ $\delta$ $\leq$ log1.0734 and log0.9674 $\leq$ $\delta$ $\leq$ log1.220 for AU $C_{t}$, and $C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Cephradine capsules (Shinpoong Pharmaceutical Co.) is bioequivalent to Cephradine capsules (Donggu Pharmaceutical Co.).o.).o.).).o.).

• Journal of Gastric Cancer
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• 제17권4호
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

• Journal of Pharmaceutical Investigation
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• 제34권4호
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• pp.311-317
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• 2004

A bioequivalence study of $Gomcillin^{TM}$ capsules (DAEWOONG Pharmaceutical Co., Korea) to $Famoxin^{TM}$ capsules (Dong Wha Pharm. Ind. Co., Korea) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the amoxicillin dose of 500 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of amoxicillin were monitored by a high-performance liquid chromatography for over a period of 8 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 8 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 effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Gomcillin^{TM}/Famoxin^{TM}$ were $log0.91\;{\sim}\;log1.03$ and $;log0.93\;{\sim}\;log1.10$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80\;{\sim}\;log1.25$. Thus, our study demonstrated the bioequivalence of $Gomcillin^{TM}$ and $Famoxin^{TM}$ with respect to the rate and extent of absorption.

• Journal of Veterinary Science
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• 제23권5호
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• pp.64.1-64.9
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• 2022

Background: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. Objectives: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. Methods: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (C_max), time to reach maximum plasma concentration (t_max), area under the concentration-time curve values (AUC_0-21d), half-life (t_1/2), and other pharmacokinetic parameters were calculated. Results: Although the highest maximum plasma concentration (C_max) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the C_max, t_max, t_1/2, MRT_{0-inf_obs}, Vz/F_obs, and Cl/F_{_obs} parameters between the experimental groups. Conclusions: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.

• 한국안광학회지
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• 제7권2호
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• pp.181-187
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• 2002

수정체는 조절력의 변화에 의해서 곡률이 변화한다. 조절력은 탄성체인 수정체에 힘을 수직으로 주는 경우 정점 방향으로 길이가 늘어난다. 힘을 받는 수정체는 밀도 분포와 형태가 후면에 치우쳐있어, 후면 방향의 수평 힘 보다 전면 방향의 수평 힘이 더 크다. 그러므로 후면 방향 보다 전면 방향의 두께가 더 많아 늘어난다. 그러나 조절력이 일정 값 보다 커지기 시작하면 전면에서는 팽창률이 한계에 도달하다. 이 때 전면 방향의 수평 힘 보다 후면 방향의 수평 힘이 더 커지게 되어, 전면 방향 보다 후면 방향의 두께가 더 많아 늘어난다. 전면과 후면의 두께변화 차이는 조절력에 대해 2차 곡선(${\Delta}=B_1D+B_2D^2$)을 이룬다. 조절력에 따른 전면과 후면의 두께(${\Delta}t_a$, ${\Delta}t_p$) 차이 변화 곡선은 다음과 같이 표현된다. $${\Delta}t_a=t_a-t_{ao}=t_{max}+t_0{\exp}(-A/B)-t_{ao}$$ $${\Delta}t_p=t_p-t_{po}=t_{min}+t_0{\exp}(A/B)-t_{po}$$ 인간의 수정체에서 구한 각각의 Parameter값은 전면에서 $t_{min}=1.1.06$, $t_0=-0.33$, B=9.32, 후면에서 $t_{max}=1.97$, $t_0=0.10$ B=7.96 등을 얻었다. 조절력에 따른 수정체의 전면과 후면에서 정점 곡률 안정의 변화는 다음과 같다. $$R=R_0+R_1{\exp}(D/k)$$ 수정체에서 구한 각각의 Parameter 값은 전면에서 $R_{min}=5.55$, $R_1=6.87$, k=4.65, 후면에서 $R_{max}=-68.6$, $R_1=76.7$, k=308.5 등을 얻었다.

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.43-49
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• 2002

The present study was conducted to investigate the placental transfer and pharmacokinetics of the flu-oroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 mg $^{14}C$ DW-116/kg on gestational day 18. Maternal and fetal tissues were collected at 0.17 0.5,1,2,4,8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16~28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The $T_{1/2,abs}$, $T_{1/2,{\beta}},$ AUC, $T_{max},$ and $C_{max}$ in the maternal plasma were approximately 6 min, 13.3 h, 1620 $ug^*hr/ml,$ 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 $ug^*h/$m\ell$,$ 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h,2549 $ug^*h/$m\ell$,$ 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the 4T_1/2,abs}$, $T1/2,{\beta},$ AUC, $T_{max},$ and $C_{max}$ were approximately 1.3 h,9.3 h,2508 $ug^*h/$m\ell$,$ 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW-116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.

• Journal of Pharmaceutical Investigation
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• 제36권4호
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• pp.277-282
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• 2006

Lisinopril is one of the angiotensin-converting enzyme inhibitors, which have been used for treatment of hypertension and heart failure. The aim of this study was to evaluate the bioequivalence of two lisinopril tablet, $Lisihexal^{\circledR}$ and $Zestril^{\circledR}$ as a test and reference, respectively. The study was came out on 28 healthy male Korean volunteers in $2{\times}2$ crossover design. An analytical method with LC-MS-MS was developed for the quantification of lisinopril and enalapril(IS) using SPE method. The condition was selective, sensitive and precise in human plasma, that was enough for the pharmacokinetic study of lisinopril. The pharmacokinetic parameters such as $AUC_t,\;AUC_{inf},\;C_{max},\;T_{max}\;and\;t_{1/2}$ were calculated and ANOVA test was used for the statistical analysis of the parameters using log transformed $AUC_t,\;AUC_{inf}\;and\;C_{max}$. $t_{1/2}$ of test and reference drugs were calculated $11.4{\pm}5.1\;and\;16.1{\pm}9.9\;hr$, respectively. The 90% confidence intervals of $AUC_t,\;AUC_{inf}\;and\;C_{max}$ were log 0.9245$\sim$log 1.0603, log 0.9270$\sim$log 1.0601 and log 0.9548$\sim$log 1.1009, within the acceptable range of log 0.8 to log 1.25 by KFDA bioequivalence criteria. Two medications of lisinopril were evaluated bioequivalent and thus may be prescribed interchangeably.

• 한국어병학회지
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• 제22권2호
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• pp.125-135
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• 2009

Oxolonic acid (OA)를 넙치(평균체중 90 g)에 1회 경구투여(15, 30 및 60 ㎎/㎏ body weight), 1회 복강주사(10 및 20 ㎎/㎏ body weight) 및 1시간동안 약욕(30 및 50 ppm)한 다음, 경시적(3시간-144시간)인 혈장내 OA의 잔류농도를 분석하였다. 15, 30 및 60 ㎎/㎏ 농도로 경구투여한 모든 시험구에서 투여 10~15시간째 각각 1.92, 2.45 및 3.72 $\mu{g}/m\ell$로 최대혈중농도를 나타내었다. 10 및 20 ㎎/㎏ 농도로 복강주사한 경우, 투여 10시간째 각각 4.1 및 4.8 $\mu{g}/m\ell$로 최대혈중농도를 나타내었다. 약욕한 시험구의 경우, 30 및 50 ppm 시험구는 각각 투여 5-30시간째 0.22 및 0.38 $\mu{g}/m\ell$로 최대혈중농도를 나타내었다. OA의 투여방법에 따른 넙치 체내 약물 혈중농도 측정결과를 바탕으로 one- compartment model로 WinNonlin program을 이용하여 OA의 흡수, 배설, 반감기 등 약물동태학적 매개변수 (parameter)를 조사하였다. 15, 30 및 60 ㎎/㎏을 경구투여한 경우, 혈장농도-시간곡선하 면적 (AUC)은 각각 70.93, 120.0 및 141.86 $\mu{g}$ $h/m\ell$, 혈중최고농도의 도달시간($T_{max}$)은 16.22, 20.39 및 17.33 h, 혈중최고농도 ($C_{max}$)는 1.61, 2.40 및 3.01 $\mu{g}/m\ell$로 계산되었다. 10 및 20 ㎎/㎏을 복강주사한 경우, 혈장농도-시간곡선하 면적(AUC)은 각 각 184.7 및 315.92 $\mu{g}$ $h/m\ell$, 혈중최고농도의 도달시간($T_{max}$)은 5.91 및 6.26 h, 혈중최고농도($C_{max}$)는 4.19 및 4.45 $\mu{g}/m\ell$로 계산되었다. 30 및 50ppm으로 약욕한 경우, 혈장농도-시간곡선하 면적 (AUC)은 각각 17.58 및 21.69 $\mu{g}$ $h/m\ell$, 혈중 최고농도의 도달시간($T_{max}$)은 19.08 및 31.43 h, 혈중최고농도($C_{max}$)는 0.22 및 0.25 $\mu{g}/m\ell$로 계산되었다.

• 한국임상약학회지
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• 제12권2호
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• pp.71-75
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• 2002

This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ (test drug, cefaclor 250 mg/capsule) with that of $Ceclor^{(R)}$ (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean adult. The bioavailability was examined on 20 healthy volunteers who received a single dose (250 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 6hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-6hr},\;C_{max},\;T_{max},\;AUC_{int},\;K_e,\;t_{1/2},\;Vd)$ F, and CL/F) were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max},\;log-transformed\;AUC_{0-6hr}\;log-transformed\;C_{max},\;t_{l/2},\;V_d/F$, and CL/F. The ratios of geometric means of AUC0-6hr and $C_{max}$ between test drug and reference drug were $103.2\%\;(6.74\;{\mu}g{\cdot}hr/ml\;vs\;6.53{\pm}g{\cdot}hr/ml)\;and\;100.4\%\;(4.85\;{\mu}g\ml\;vs\;4.82\;{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug were $0.9\pm0.38\;hr\;and\;0.83\pm0.34$ hrs, respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-6h},\;and\;C_{max}$ were log $0.98{\sim}log$ 1.08 and log $0.88{\sim}log1.15$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The estimated half-life of this study was longer $(1.21\pm0.27\;hrs\;vs\;0.5-1\;hr)$, the Vd/F was larger $(68.89\pm25.72L$ vs 24.9L), and the CL/F was higher $(38.62\pm7.09\;L/hr$ vs 24.9 L/hr) than the previously reported values.

• 대한수학회지
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• 제38권1호
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• pp.177-191
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• 2001

We consider a linear differential game described by the delay-differential equation in a Hilbert space H; (※Equations, See Full-text) U and V are Hilbert spaces, and B(t) and C(t) are families of bounded operators on U and V to H, respectively. A(sub)0 generates an analytic semigroup T(t) = e(sup)tA(sub)0 in H. The control variables g, and u and v are supposed to be restricted in the norm bounded sets (※Equations, See Full-text). For given x(sup)0 ∈ H and a given time t > 0, we study $\xi$-approximate controllability to determine x($.$) for a given g and v($.$) such that the corresponding solution x(t) satisfies ∥x(t) - x(sup)0∥ $\leq$ $\xi$($\xi$ > 0 : a given error).