• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.413-419
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• 2008

Carvedilol, is a nonselective $\beta$-blocking agent and it also has vasodilating properties that are attributed mainly to its blocking activity at ${\alpha}_1$-receptors. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{(R)}$ tablet 12.5 mg (Chong Kun Dang Pharmaceutical Co., Ltd.) and Cadilan tablet 12.5 mg (KyungDong Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of carvedilol from the two carvedilol formulations in vitro was tested using KP VIII Apparatus II method with pH 4.5 dissolution medium. Thirty two healthy male subjects, $25.00{\pm}3.09$ years in age and $70.71{\pm}11.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 12.5 mg as carvedilol was orally administered, blood samples were taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Dilatrend^{(R)}$ tablet 12.5 mg, were 4.66%, 8.33% and -7.45% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $\log\;0.9823{\sim}\log\;1.1042$ and $\log\;1.0132{\sim}\log\;1.1875$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Cadilan tablet 12.5 mg was bioequivalent to $Dilatrend^{(R)}$ tablet 12.5 mg.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.289-295
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• 2001

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

• 한국산학기술학회논문지
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• 제11권7호
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• pp.2451-2458
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• 2010

고혈압 치료제인 카르베딜롤을 모델약물로 하여 새로운 서방성 방출 제어형 매트릭스 정제를 제조하기 위하여 소수성 서방성 부형제인 Compritol 888 ATO와 친수성 고분자인 hydroxypropyl methyl cellulose (HPMC) 또는 polyethylene oxide (PEO)를 이용하여 방출 제어형 매트릭스 정제를 제조하였다. 카르베딜롤 방출 제어형 매트릭스 정제의 제조 시 Compritol 888 ATO의 비율과 친수성 고분자의 종류 및 비율, hot melt coating coagglutination (HMCC) rocess의 적용 유무에 따른 카르베딜롤의 방출 양상을 위하여 용출시험기를 사용하여 pH 1.2의 인공위액과 pH 6.8의 인공장액에서 24시간 동안 $37^{\circ}C$, 50 rpm으로 용출시험을 실시하였다. 그 결과, HMCC process를 적용한 모든 제제가 약물의 방출 제어에 매우 효과적인 것을 확인하였다. 또한 소수성 서방성 부형제인 Compritol 888 ATO의 비율에 따라 약물의 방출 양상 및 시간이 기존 일반정제에 비하여 약 95%의 용출률을 나타내었으며 24시간까지 지연됨을 확인할 수 있었다.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2009년도 춘계학술대회
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• pp.216-216
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• 2009

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.220.1-220.1
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• 2003

A sensitive and selective liquid chromatographic method for the determination of carvedilol in human plasma was developed and validated. Analytes were separated on a XTerra C18 column with acetonitrile-methanol-30 mM KH$_2$PO$_4$ (pH 2.5) (20 : 20 : 60, v/v/v), as mobile phase. One mL plasma were pipetted into glass tubes and spiked with 0.05 mL of internal standard solution. After adding 7 mL of diethyl ether, the plasma sample was then shacked for 15 min. A centrifuged upper layer was back-extracted with 150 uL of 0.05 M sulfuric acid. (omitted)

• 한국임상수의학회지
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• 제41권2호
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• pp.95-100
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• 2024

A 6-year-old neutered male Poodle with a body weight of 2.7 kg was diagnosed with a congenital extrahepatic portoazygos shunt presented with progressive hepatic encephalopathy. Five days after surgical attenuation, the patient showed post-attenuation neurological signs (PANS) such as generalized tonic-clonic seizure, dull mentation, and tremor. PANS were successfully managed with antiepileptic drugs, but third-space fluid accumulation (ascites and peripheral edema) and phlebectasia were newly identified, suggesting marked portal hypertension (PHT). Telmisartan, spironolactone, carvedilol, and prednisolone were sequentially administered. Three months after surgery, both abnormal clinicopathological values such as anemia and hypoalbuminemia, and clinical signs completely resolved. Herein, we report successful management strategies for PANS and PHT in a dog following surgical attenuation of a congenital portoazygos shunt.