• BMB Reports
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• 제37권5호
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• pp.603-611
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• 2004

Fluorescence probes located in different membrane regions were used to evaluate the effects of chlorpromazine HCl on structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and lipid bilayer thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. The experimental procedure was based on the selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In this study, chlorpromazine HCl decreased the lateral mobility of Py-3-Py in a concentration dependent-manner, showed a greater ordering effect on the inner monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the drug was found to have a clustering effect on membrane proteins.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.53-58
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 180 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Hanmi Fexofenadine Hydrochloride $Tablet^{\circledR}$ made by Hanmi Pharm. Co. and the reference product was Allegra $Tablet^{\circledR}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2\;{\time}\;2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were $log\;0.822{\sim}log \;1.142$ and $log\;0.848{\sim}log\;1.172$, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet is bioequivalent to Allegra Tablet.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.231-236
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• 1995

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excisicylic acid were investigated. In-vitro experiment using a Franze-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inoraganic anions were rougly proportional to lyotropic Hofmeister serlling abilities of the anions l F/sup -/

• 한국동물학회지
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• 제32권1호
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• pp.34-39
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• 1989

젖산수소이탈효소 동위효소의 상대적값을 변화시키기 위하여 ouabain, strychnine sulfate, caffeine sodium benzoate 및 chlorpromazine hydrochloride을 웅성 mouse에 7일, 14일 및 21일간 복강주사하였다. 뇌, 심장 및 신장조직의 이 효소를 셀룰로우즈 strip상에서 전기영동한 후 densitometry에 의하여 동위효소들의 상대적 값을 구하였다. Ouabain은 뇌좆기에서만 B$_4$동위효소를 급격히 증가시켰다. 두가지 stimulant들은 뇌조직에서 $A_4$및 B$_4$동위효소의 상대적 값을 뚜렷하게 변화시킨 반면 deprossant는 뇌조직과 심장조직의 B$_4$동위효소를 제외하고는 동위효소의 재분포를 유도시키지 않았다. 이러한 실험적 결과들로부터 Na+ 이온이나 Ca++ 이온들의 세포질내 농도변화는 젖산수소이탈효소 동위효소의 재분포의 원인이 되지 않으며 원형질막의 체제가 이 효소의 조직특이성을 나타나게 하는 한가지 요인이 될 수 있다고 사료된다.

• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.99-105
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• 2000

This study compared the permeability of $[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ through the blood-brain barrier (BBB) in mice and rats with common carotid artery perfusion (CCAP) method that modified internal carotid artery perfusion (ICAP) method. External carotid artery (ECA) was cannulated with coagulating pterygopalatine artery (PPA) in ICAP method, while CCA was cannulated without coagulating PPA in CCAP method. Also, for evaluation of BBB permeability of drugs in mice and rats, we used intravenous injection technique. The results of CCAP method in mice at a perfusion flow-rate of 2 ml/min, the brian volume of distribution $(V_D)$ of $[^{14}C]sucrose,\;[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ were similar to the result of ICAP method in rats at perfusion flow rate of 4 ml/min. The area under the plasma concentration-time curve and brain uptake of $[^3H]taurine$ by intravenous injection technique, were $65.5{\pm}9.7%ID^*min/ml\;and\;0.515{\pm}0.093%ID/g$, respectively, in mice, and the corresponding values were $8.00{\pm}0.03%ID^*min/ml\;and\;0.052{\pm}0.003%ID/g$ in rats. But the BBB permeability surface-area product of $[^3H]taurine$ was similar between mice and rats. In conclusion, the CCAP method in mice was simple, fast and comparable to ICAP method in rats for drug permeability through the BBB.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.499-504
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• 2004

Paroxetine, a potent and selective serotonine reuptake inhibitor, has been used for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. The bioequivalence of two paroxetine preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Samchully Paroxetine $tablet^{\circledR}$ made by Samchully Pharm. Co. and the reference product was Seroxat $tablet^{\circledR}$ made by GlaxoSmithKline. Twenty healthy male subjects, $22.4{\pm}2.6$ years old and $63.8{\pm}4.2\;kg$, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 20 mg paroxetine was orally administered, blood was taken at predetermined time intervals and the concentration of paroxetine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.84-log 1.16 and log 0.85-log 1.14, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Samchully Paroxetine tablet is bioequivalent to Seroxat tablet.

• Journal of Veterinary Science
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• 제21권5호
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• pp.60.1-60.11
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• 2020

Background: Tumor-associated neoangiogenesis is a crucial target for antitumor therapies. Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies in dogs. Objectives: The aim of the study was to assess the pharmacokinetics of TAL after single oral administration in dogs. Additionally, the influence of feeding on the pharmacokinetic profile of TAL in dogs has been preliminarily investigated. Methods: Six healthy adult female Labradors were enrolled according to a randomized single-dose, 2-treatment, 2-phase, paired 2 × 2 cross-over study design. The dogs were administered a single 400 mg capsule of TAL in fasted and fed conditions. Blood was collected from 15 min to 48 h after dosing, and TAL quantified in plasma by a validated high-performance liquid chromatography method. The pharmacokinetics of TAL were analyzed using a non-compartmental approach. Results: TAL concentration was quantifiable up to 10 h and 24 h after fasted and fed conditions, respectively. C_max (fasted, 1.34 ± 0.12 ㎍/mL; fed, 2.47 ± 0.19 ㎍/mL) and T_max (fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t_1/2λz were significantly higher in fed (42.46 ± 6.64 mg × h/L; 17.14 ± 4.68 h) compared to fasted (12.38 ± 1.13 mg × h/L; 6.55 ± 1.25 h) dogs. The relative oral bioavailability of TAL for the fasted group was low (36.92% ± 3.28%). Conclusions: Feeding affects the pharmacokinetics of oral TAL in dogs, showing a delayed, but higher absorption with different rate of elimination. These findings are of importance in clinical veterinary settings, and represent a starting point for further related studies.

• 핵의학기술
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• 제25권2호
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• pp.35-40
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• 2021

신사구체여과율(glomerular filtration rate, GFR)은 신장 질환의 진단, 치료 및 추적 관찰에 중요한 지표이며, 건강인에서도 약제사용, 신장이식 공여자의 신장 평가 등에 사용된다. GFR 검사의 표준방법은 외인성 표지자인 이눌린(inulin)을 연속 주입하여 측정하는 방법이나, 시간이 많이 소요되고 검사 방법이 복잡하기 때문에, 혈청 크레아티닌 농도로 계산한 추정사구체여과율(estimated glomerular filtration rate, eGFR)을 대신 사용한다. 그러나 크레아티닌은 연령, 성별, 근육량 등에 영향을 받는 것으로 알려져 있으며, 현재 많이 사용되는 추정사구체여과율 공식에는 성인의 경우 Cockroft-Gault 공식, Modification of Diet in Renal Disease(MDRD) 공식, Chronic kidney Disease Epidemiology Collaboration (CKD-EPI) 공식 등이 있고, 소아의 경우 Schwartz 공식을 사용하고 있다. ^99mTC diethylenetriaminepentaacetic acid(^99mTc-DTPA)를 사용한 신사구체여과율(glomerular filtration rate, GFR) 측정은 이눌린을 대체 할 수 있어 현재 사용되고 있다. 이에 ^99mTc-DTPA를 이용하여 측정한 신사구체 여과율과 CKD-EPI 공식을 이용한 추정사구체여과율을 비교하여 보았다. 서울 아산병원을 내원한 신장이식 공여자 200명(남성 96명, 여성 104명, 47.3세±12.7)을 대상으로 ^99mTc-DTPA(0.5 mCi, 18.5 MBq)를 정맥투여 하고 획득된 plasma(Two-plasma-sample-method, TPSM)를 계측하여 신사구체여과율(glomerular filtration rate, GFR)을 측정하였다. 혈청 크레아티닌 농도를 근거로 chronic kidney disease epidemiology collaboration (CKD-EPI) 공식을 이용하여, 추정사구체여과율(estimated glomerular filtration rate, eGFR)을 도출하였다. 신장이식 공여자 200명(남성 96명, 여성 104명, 47.3세±12.7)을 대상으로 ^99mTc-DTPA를 사용하여 측정된 신사구체여과율 평균값은 97.27±19.46 (GFR, ml/min/1.73m²)이고 CKD-EPI 공식을 이용한 추정사구체여과율 (estimated glomerular filtration rate, eGFR) 평균값은 96.84±17.74(CKD-EPI, ml/min/1.73m²), 혈청 크레아타닌의 농도는 0.84±0.39 (mg/dL)이다. 혈청 크레아티닌 근거 추정사구체여과율에 대한 ^99mTc-DTPA 신사구체여과율의 회귀식은 Y= 0.5073X + 48.186, 상관계수는 0.698이었다.(P<0.01)혈청 크레아티닌 근거 추정사구체여과율에 대한 ^99mTc-DTPA 신사구체여과율의 Difference(%)는 1.52±18.28 이었다. ^99mTC-DTPA를 이용해서 측정된 신사구체여과율과 혈청 크레아티닌 농도에 기반하여 도출된 추정사구체여과율에 대한 상관계수는 0.698로 중등도 정도의 상관성을 확인할 수 있었다. 이는 추정사구체여과율은 연령, 성별, 근육 양 등 신장 외적인 요소에 영향을 받고 신장질환자를 대상으로 만든 공식을 사용하는 원인에 기인하는 것으로 추정된다. 신장 질환의 진단, 치료 및 추적 관찰, 신장이식 공여자의 신장 평가 등에 사용되는 신사구체여과율 측정에 ^99mTc-DTPA를 사용함으로써 신뢰성 있는 결과를 임상에 제공할 수 있다.

• 대한수의학회지
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• 제32권1호
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• pp.35-39
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• 1992

Sulfamethazine(SMZ)은 수의임상에서 감염증 치료 및 예방목적으로 많이 사용되고 있을 뿐 아니라 가축의 생산성 향상을 위해 남용되고 있는 주요한 항균제의 하나이다. SMZ의 생체내 대사 및 약물동태학적 특성은 동물의 종차에 따라 상이함이 잘 알려져 있으나 주요 실험동물 및 경제동물인 토끼에서 조사된 바는 매우 드물다. 한편 성차에 따른 약물대사의 차이는 rat를 비롯한 여러 동물에서 인정되고 있는데 대체로 숫컷이 암컷에 비해 대사능이 활발한 것으로 알려져 있다. 그러나 산양에서의 SMZ의 대사는 오히려 암컷이 더 활발하다는 보고도 있어, 여러 동물종에서 일률적으로 성차에 따른 약물대사를 설명할 수가 없다. 초식성의 습성을 가지고 있는 토끼에 있어 성차에 따른 SMZ의 대사 및 약물동태학적 특성이 다른 초식성 동물인 산양의 경우와 동일한 경향을 보이는지는 매우 흥미 있다할 것이다. New Zealand White 토끼에 SMZ을 이정맥에 35mg/kg를 주사한 후 미리 정해진 시간에 수거된 혈장 및 뇨(24시간)를 HPLC를 이용하여 분석하여 아래와 같은 약물동태학 및 대사적 특성을 얻었다. 1. 토끼에서의 SMZ의 주요 대사경로는 아세틸화$(N_4AcSMZ)$이었다. 두개의 수산화 대사산물(50HSMZ, $6CH_2OHSMZ$)도 생성되어 수산화 경로가 있음을 확인하였으나 양적인 관심에서 주요하지 않았다. 2. 토끼에서의 SMZ의 각 대사산물의 생성은 암수간의 성차에 따른 차이가 인정되지 않았다. 3. SMZ을 토끼의 이정맥에 투여(35mg/kg)하였을 때의 약물동태학적 특성은 1구1차 지수형 배설형태로 설명이 가능하였으며 암수에 따른 성차가 인정되지 않았다. 4. SMZ는 신속하게 $N_4AcSMZ$로 대사되었으며, $N_4AcSMZ$의 체외배설은 SMZ에 비해 매우 느렸으며 성차에 따른 배설속도의 차이를 인정할 수 없었다.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.335-342
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• 2008

The bioequivalence of two carbamazepine preparations was conducted. The in vivo bioequivalence study in 20 healthy male Korean volunteers was designed by using a single dose, randomized, 2-period crossover with a 3-weeks washout period between the doses. Prior to the in vivo study, an in vitro comparative dissolution test was performed by the paddle and basket method as described in the bioequivalence guidance of the Korea Food and Drug Administration (KFDA). Based on the similar dissolution pattern between two preparations in the dissolution test, the two formulations are demonstrated to be pharmaceutically equivalent. In addition, in vivo bioequivalence test was used to reconfirm the in vitro dissolution results. In the in vivo bioequivalence study, the plasma concentrations of carbamazepine up to 144 h after the administration were determined using a validated HPLC method with UV detection and the bioequivalence between the two drug products was assessed by statistical analysis of the log transformed mean ratios of $C_{max}$, $AUC_{0-t}$ and $AUC_{0-\infty}$. The mean maximum concentration ($C_{max}$) of the test and reference were found to be $1467.0{\pm}335.8\;ng/mL$ and $1465.9{\pm}310.3\;ng/mL$, respectively. The 90% confidence intervals (C.I.) of $C_{max}$ were in the range from 0.95 to 1.05. As for the $AUC_{0-t}$ and $AUC_{0-\infty}$, test values were $110027.1{\pm}27786.4\;ng/mL{\cdpt}h$, $128807.0{\pm}34563.2\;ng/mL{\cdot}h$ and $105473.6{\pm}26496.2\;ng/mL{\cdot}h$, $125448.5{\pm}35975.5\;ng/mL{\cdot}h$, respectively. The 90% C.I. of $AUC_{0-t}$ were 0.97 to 1.10 and of $AUC_{0-\infty}$, 0.99 to 1.09 and thus were within the log 0.8-log 1.25 interval proposed by the KFDA. A two-way ANOVA showed no significant difference between the two formulations. Based on these statistical analysis, it was concluded that the test formulation is bioequivalent to the reference.