• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.85-90
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• 2004

Bisoprolol, one of the $\beta_1-adrenorecepter$ antagonist, has been used for the treatment of mild to moderate essential hypertension anti stable angina pectoris. The oral bloavailability of bisoprolo1 is high $(90\%)$ and the drug has a long elimination half-life, $9{\sim}12\;hr$, which allows once-daily administration. The bioequivalence of two bisoprolol preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Concor $tablet^{(R)}$ made by Newgenpharm and the reference product was Monocor $tablet^{(R)}$ made by Wyeth Korea. Twenty healthy male subjects, 23.8 (21-30) years old and 03.8(52-92) kg, were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After two tablets containing 10 mg bisoprolol hemifumarate were orally administered, blood was taken at predetermined time intervals and the concentration of bisoprolol in plasma was determined using an HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$ were calculated and analyzed statistical]y 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 $0.95{\sim}1og\;1.04\;and\;1og\;0.96{\sim}1og\;1.07,\;respectively.$ These values were within the acceptable bioequivalence intervals of log $0.8{\sim}log\;1.23$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Concor tablet is bioequivalent to Monocor tablet.

• Korean Journal of Clinical Pharmacy
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• v.12 no.2
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• pp.96-100
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• 2002

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.117-126
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• 1999

Differential scanning calorimetry(DSC) was used as a screening technique for assessing the compatibility of some drugs with excipients. On the basis of DSC results, interaction of ibuprofen with PVP K40 was found and eutectic formations with PEG 6000 or magnesium stearate were demonstrated. Fenoprofen Ca was found to interact with PEG 6000. Naproxen showed interactions with PEG 6000, PVP K40, PVPP and Mg stearate. Interactions of tiaprofenic acid with PVP K40 or PVPP were found and eutectic formations with PEG 6000 or Mg stearate were observed. Bisoprolol hemifumarate, metoprolol tartrate and penbutolol sulfate were found to interact with lactose.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.402-406
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• 2001

Gas chromatographic method was investigated for the chiral separation of several $\beta$-blockeros(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-$\alpa$-methoxy-$\alpa$-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted into O-silyl ethers by react with N-methyl-H-(taimethylsilyl)trifluoroacetamide. The reaction was selective and rapid and the diasteromeric derivatives were well separated by capillary gas chromatography. (R)-isomers were eluted faster than (S)-isomers when (-)-$\alpa$-methoxy-$\alpa$-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-$\alpa$-methoxy-$\alpa$-(trifluoromethyl)phenylacetyl chloride was used. No racemization was found during the reaction.

• YAKHAK HOEJI
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• v.47 no.4
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• pp.200-205
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• 2003

The stability constants for the inclusion complexes between carboxymethyl-$\beta$-cyclodextrin (CM-$\beta$-CD) and five $\beta$-blockers, such as atenolol (ATE), bisoprolol (BIS), metoprolol (MET), pindolol (PIN) and propranolol (PRO) were determined by capillary electrophoresis. The magnitude of stability was decreased as following order; PRO＞MET＞BIS＞ATE＞PIN. Among them PRO showed the highest affinity towards CM-$\beta$-CD with stability constants of 383 and 371 $M^{-l}$ for (R)- and (S)-enantiomer, respectively. PIN enantiomers showed the lowest stability towards CM-$\beta$-CD, while the selectivity between (R)- and (S)-enantiomer was higher than any other tested $\beta$-blocker.r.

• Archives of Pharmacal Research
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• v.22 no.6
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• pp.608-613
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• 1999

Optimum conditions of chiral derivatization reaction of $\beta$-blockers (acebutolol, arotinolol, betaxolol, bisoprolol, celiprolol, metoprolol and pindolol) with (-)-menthyl chloroformate were investigated for the resolution by HPLC. With more than 30 times molar excess of (-)-methyl chloroformate chiral derivatization reactions were completed within one hour at room temperature except arotinolol and celiprolol. Diastereomeric derivatives of $\beta$-blockers were well resolved on the ODS column using acetonitrile-methanol-water as a mobile phase.

• Journal of the Korean Society of Manufacturing Process Engineers
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• v.19 no.10
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• pp.8-15
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• 2020

The diffusion cell method is the main technique employed for the in vitro diffusion test of transdermal drug delivery preparations. Most existing transdermal diffusion devices use a water bath heating structure and direct current motor magnetic stirrer. However, these devices are confronted with problems, such as large volume, incompatible vertical and horizontal diffusion cells, few diffusion cell sets, and poor reliability. To overcome these deficiencies, the system adopts a dry heating method and uses a rotating magnetic field generated by the electromagnetic stirrer to drive the magnetic stirrer. Accordingly, the resulting device is characterized by a simple structure and small volume, convenient operation, compatible vertical and horizontal diffusion cells, and numerous diffusion cell sets. The reliability and practicability of the system is verified by the in vitro percutaneous permeability test of the bisoprolol patch.

• Journal of Radiation Industry
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• v.10 no.4
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• pp.181-187
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• 2016

Selective ${\beta}_1$-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective ${\beta}_1$-antagonists including nebivolol have high binding affinity on ${\beta}_1$-adrenergic receptor, not ${\beta}_2$-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective ${\beta}_1$-blockers in clinically used ${\beta}_1$-blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective ${\beta}_1$-blocker. Nebivolol is $C_2$-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of $^{18}F$. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for $^{18}F$-aromatic substitution, was synthesized in moderate yield which was readily subjected to $^{18}F$-aromatic substitution to give $^{18}F$-labelled nebivolol.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.47-47
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• 1992

$\beta$수용체에 대한 차단약으로 propranolol이 1964년에 도입된 후, 현재까지 수십여종의 $\beta$-차단약이 개발되었다. 그중 특이 $\beta$1 수용체에 대해 선택적인 억제효과를 지닌 atenolol, metoprolol, betaxolol, celiprolol 및 최근에 bisoprolol 등이 개발되어 임상적으로 부정맥, 협심증, 고혈압의 치료에 사용되고 있다. 그 작용기전으로는 심박출량의 감소, renin 유리억제, 중추억제효과 등이 제시되고 있으나, 이들의 약효검색은 주로 $\beta$1수용체가 많이 존재하는 심장에 대한 억제효과를 중심으로 실시한다. 즉, SHR 및 개를 사용한 생체실험과 심장, 심방 ($\beta$1) 및 기완지, 혈관($\beta$2)을 이용한 적출장기실험을 통하여 isoproterenol에 대한 억제효과를 용량반응 곡선으로 그리고, Van rossum 법에 의해 pA$_2$ 치를 구하여 $\beta$-차단제의 효력을 평가한다. 특히, pA$_2$ 치가 클수록 $\beta$-차단제의 효력이 큰 약물이다. 또한 수용체 결합실험으로 소의 심실 세포막을 분리하여 $^3$H-DHA 와의 결합실험을 통해 해리항수(Kd) 를 측정하고, 이어서 $^3$H-DHA의 일정농도와 함께 미지의 $\beta$-차단제를 여러 농도로 변화시켜 가하여 치환곡선을 작성한다. 여기에서 얻은 치환약의 $IC_{50}$/ 치로부터 치환약의 해리항수(Ki)를 산출한다. 이때 약물과 수용체의 친화력은 해리항수의 역수이므로 해리항수가 적을수록 $\beta$ 수용체에 대한 친화력이 큰 약물이다. 시사되었으며, 이 조직에서 또한 5-$HT_2$와 5-$HT_3$ 수용체의 존재를 확인하고 각각의 기능을 분명히 했다.가 수월하게 하였고 메모리를 동적으로 관리할 수 있게 하였다. 또한 기존의 smpl에 디버깅용 함수 및 설비(facility) 제어용 함수를 추가하여 시뮬레이션 프로그램 작성을 용이하게 하였다. 예를 들면 who_server(), who_queue(), pop_Q(), push_Q(), pop_server(), push_server(), we(), wf(), printfct() 같은 함수들이다. 또한 동시에 발생되는 사건들의 순서를 조종하기 위해, 동시에 발생할 수 있는 각각의 사건에 우선순위를 두어 이 우선 순위에 의하여 사건 리스트(event list)에서 자동적으로 사건들의 순서가 결정되도록 확장하였으며, 설비 제어방식에 있어서도 FIFO, LIFO, 우선 순위 방식등을 선택할 수 있도록 확장하였다. SIMPLE는 자료구조 및 프로그램이 공개되어 있으므로 프로그래머가 원하는 기능을 쉽게 추가할 수 있는 장점도 있다. 아울러 SMPLE에서 새로이 추가된 자료구조와 함수 및 설비제어 방식등을 활용하여 실제 중형급 시스템에 대한 시뮬레이션 구현과 시스템 분석의 예를 보인다._3$", chain segment, with the activation energy of carriers from the shallow trap with 0.4[eV], in he amorphous regions.의 증발산율은 우기의 기상자료를 이용하여 구한 결과 0.05 - 0.10 mm/hr 의 범위로서 이로 인한 강우손실량은 큰 의미가 없음을 알았다.재발이 나타난 3례의 환자를 제외한 9례 (75%)에서는 현재까지 재발소견을 보이지 않고 있다. 이러한 결과는 다른 보고자들과 유사한 결과를 보이고 있지만 아직까지 증례가 많지 않기 때문에 생존율을 얻기에는 미흡한 점이