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

• 한국임상약학회지
• /
• 제18권1호
• /
• pp.38-44
• /
• 2008

Rebamipide, ($\pm$)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{(R)}$ (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide 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, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % 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 0.84$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.

• 약학회지
• /
• 제47권5호
• /
• pp.339-344
• /
• 2003

Atenolol is a water soluble, ${\beta}_1$ selective adrenoceptor antagonist used in the treatment of angina and hypertension. It is primarily eliminated renally with minimal hepatic metabolism. The purpose of the present study was to evaluate the bioequivalence of Samchundang Atenolol (Samchundang Pharmaceutical Co., Korea.) to Tenolmin(Hyundai Pharmaceutical Ind. Co., Korea). The atenolol release from the two atenolol 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 and water). Twenty four normal male volunteers, 22.83$\pm$1.99 years in age and 65.82$\pm$7.15 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 50 mg of atenolol was orally administered, blood was taken at predetermined time intervals and the concentrations of atenolol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two atenolol 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 logarithmically transformed $AUC_{t}$ and $C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_{t}$, $C_{max}$ and $T_{max}$ between two tablets based on the Tenolmin were 3.74％, 4.38％ and 17.77％, respectively. There were no sequence effects between two tablets 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(0.98)∼log(1.l1) and log(0.95)∼log(1.l5) for $AUC_{t}$ and $C_{max}$ respectively), indicating that Samchundang Atenolol tablet is bioequivalent to Tenolmin tablet.

• 한국임상약학회지
• /
• 제12권1호
• /
• pp.22-28
• /
• 2002

Aceclofenac, 2-[(2',6'-dichlorphenyl)amino]phenylacetoxiacetic acid, is a new nonsteroidal anti-inflammatory drug that belongs to the family of phenylacetic acids. It shows good tolerance and potent analgesic/antiinflammatory properties, and acts on cartilaginous chondriocytes, stimulating their repair mechanism. The purpose of the present study was to evaluate the bioequivalence of two aceclofenac products, $Airtal^{TM}$ tablet (Daewoong Pharmaceutical Co.) and $Acer^{TM}$ capsule (Kyungdong Pharmaceutical Co.), according to the guideliner of Korea Food and Drug Administration (KFDA). The aceclofenac release from the two aceclofenac products in vitro was tested using KP VII Apparatus II method at pH 7.8 dissolution media. Sixteen normal male volunteers, $23.13\pm2.03$ years in age and $66.33\pm7.08$ kg in body weight, were divided into two groups and a randomized $2\times2$ cross-over study was employed. After one tablet or capsule containing 100 mg of aceclofenac was orally administered, blood was taken at predetermined time intervals and the concentrations of aceclofenac in serum were determined using HPLC with UV detector. The dissolution profiles of the two aceclofenac products were very similar at pH 7.8 dissolution media. 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. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two products were $6.50\%,\;-1.06\%\;and\;11.96\%$ respectively, when calculated against the $Airtal^{TM}$ tablet. The powers $(1-\beta)\;for\;AUC_t,\;C_{max}\;were\;89.82\%\;and\;82.84\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%\;(e.g.,\;17.51\%\;and\;19.30\%\;for\;AUC_t,\;C_{max}$, ). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-3.73\%\sim16.73\%\;and\;-12.34\%\sim10.22\%\;for\;AUC_t,\;C_{max},\;respectively)$. Two parameters met the criteria of KFDA for bioequivalence, indicating that $Acer^{TM}$ capsule is bioequivalent to $Airtal^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
• /
• 제34권2호
• /
• pp.139-145
• /
• 2004

The purpose of the present study was to evaluate the bioequivalence of two risperidone tablets, Risperdal (Janssen Korea Co., Ltd.) and Rispen (Myung In Pharm. Co., Ltd), according to the guidelines of Korea Food and Drug Administration (KFDA). The risperidone release from the two risperidone formulations in vitro was tested using KP VIII Apparatus II method with various of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four healthy male subjects, $23.33\;{\pm}2.10$ years in age and $69.24{\pm}8.05\;kg$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross over study was employed. After one tablet containing 2 mg as risperidone was orally administered, blood was taken at predetermined time intervals and the concentrations of risperidone in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were 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 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 Risperdal were 0.20, -1.29 and -11-09% for $AUC_t$,$C_{max},\;and\;T_{max}$, respectively There were no sequence effects two formulations in parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g.,$log(0.90){\sim}log(1.30)$ and $log(0.84){\sim}log(1.09)$ for$AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Rispen tablet and Risperdal tablet were bioequivalent.

• Journal of Pharmaceutical Investigation
• /
• 제34권2호
• /
• pp.147-153
• /
• 2004

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, $Amaryl^{\circledR}$ (Handok/Aventis Pharm. Co., Ltd.) and Glimed (Kuhn II Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The glimepiride release from the two glimepiride formulations in vitro was tested using KP VIII Apparatus II method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB 80 into each dissolution medium). Twenty six healthy male subjects, $22.65{\pm}2.19$ years in age and $66.55{\pm}8.85$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross-over study was employed. After one tablet containing 2 mg as glimepiride was orally administered, blood was taken at predetermined time intervals and the concentrations of glimepiride in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were 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 logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Amaryl were -3.70, -8.28 and 0.61% 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., $log(0.84){\sim}log(1.04)$ for $log(0.82){\sim}log(1.03)$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Glimed tablet and Amaryl tablet were bioequivalent.

• 한국식품영양과학회지
• /
• 제20권5호
• /
• pp.479-482
• /
• 1991

고로쇠 수액의 주된 양이온 함량분포는 $Ca^{++},\;K^{+},\;Mg^{++},\;Na^{+}$이 각각 3.19, 1.74, 0.37, 0.24mEq/l이고 그 중 Ca와 K가 major ion이다. 주된 음이온은 ${SO_4}^{--}$가 2.0mEq/l, $Cl^{-}$이 0.19mEq/l 검출 되었다. 거제수 수액은 $K^{+},\;Ca^{++},\;Mg^{++),\;Na^{+}$이 각각 3.89, 1.95, 0.47, 0.42mEq/l로서 $K^{+}$의 비율이 월등히 높고 다음은 $Ca^{++}$ 순위이다. 음이온은 ${SO_4}^{--}$가 1.84mEq/l, $Cl^{-}$이 0.45mEq/l로서 ${SO_4}^{--}$가 높다. 이 양수액의 $K^{+},\;Ca^{++}와\;{SO_4}^{--},\;Cl^{-}$농도 상호간의 비율을 비교시 거제수가 고로쇠보다 $K^{+}$의 비율이 높고 $Ca^{++}$량은 상대적으로 적은 반면 ${SO_4}^{--}$는 고로쇠와 거의 비슷한 값이다. Sugar함량에서 고로쇠가 sucrose 2.7%함유로 비교적 감미가 높고 거제수는 포도당과 과당이 각각 0.097%, 0.305%함유되어 있다. 미량원소는 Cu, Zn, Mn에서 고로쇠와 거제수가 각각 0.057~3.038mg/l, 0.483~1.584mg/l, 5.507~4.354mg/l이고 거제수에서 Fe가 2.511mg/l 검출되었다.

• 약학회지
• /
• 제52권3호
• /
• pp.195-200
• /
• 2008

Gabapentin, [1-(aminomethyl) cyclohexaneacetic acid], a structural analog of $\gamma$-aminobutyric acid (GABA), is being developed for the treatment of epilepsy. Unlike GABA, gabapentin crosses the blood-brain barrier after systemic administration. Gabapentin is an effective antiepileptic drug in patients with partial and secondarily generalized seizures who are uncontrolled with use of existing anticonvulsant drug therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin 400 mg capsules, $Neurontin^{(R)}$ capsule 400 mg (Pfizer Inc.) and Gabatin capsule 400 mg (Korean Drug Co. Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, 23.58$\pm$1.50 years in age and 66.74$\pm$8.31 kg in body weight, were divided into two groups and a randomized 2$\times$2 cross-over study was employed. After one capsule containing 400 mg as gabapentin were orally administered, blood was taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, 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, $Neurontin^{(R)}$ capsule 400 mg, were 2.04, -3.68 and 16.79% 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 0.91$\sim$log 1.16 and log 0.87$\sim$log 1.11 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabatin capsule 400 mg was bioequivalent to $Neurontin^{(R)}$ capsule 400 mg.

• 약학회지
• /
• 제52권3호
• /
• pp.188-194
• /
• 2008

Fexofenadine, ($\pm$)-4-1-hydroxy-4-{4-(hydroxydiphenylmethyl)-1-piperidinyl}-butyl-a,a-dimethyl benzeneacetic acid, is a selective histamine $H_1$ receptor antagonist, and is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria as a first-line therapeutic agent. The purpose of the present study was to evaluate the bioequivalence of two fexofenadine hydrochloride tablets, $Allegra^{(R)}$ (Handok Pharmaceuticals Co., Ltd.) and Alecort (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of fexofenadine from the two fexofenadine hydrochloride formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media. Twenty six healthy male subjects, 25.62$\pm$3.35 years in age and 70.05$\pm$11.71 kg in body weight, were divided into two groups and a randomized 2$\times$2 cross-over study was employed. After a single tablet containing 120 mg as fexofenadine hydrochloride was orally administered, blood samples were taken at predetermined time intervals and the concentrations of fexofenadine in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The harmacokinetic 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, $Allegra^{(R)}$, were -1.37, 5.22 and 16.50% 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 0.83$\sim$log 1.08 and log 0.81$\sim$log 1.03 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Alecort tablet was bioequivalent to $Allegra^{(R)}$ tablet.

• Biomolecules & Therapeutics
• /
• 제16권2호
• /
• pp.168-172
• /
• 2008

The present study is to determine of sensitive nicorandil analysis method using HPLC and measure the pharmacokinetics parameters (bioavailability, $C_{max}$, $T_{max}$, Ke, $T_{1/2}$) of nicorandil (5 mg, Tab; Choongwae Pharma Corporation). Plasma (500 ul) was mixed with furosemide (internal standard, 500 ug/ml). Detection wavelength was 256 nm. The mixture of 0.01 M ammonium acetate and acetonitrile 80:20 (v/v) was used mobile phase. The HPLC separation was accomplished on ODC reverse HPLC column. The nicorandil was analyzed by a HPLC system, which consists of CAPCELL PAK C18 column (5 ${\mu}$m, 4.6 × 150 mm) and a chromatography data analysis S/W, using a isocratic mobile phase (mixture of 0.01 M ammonium acetate and acetonitrile 80:20 ) at 1.0 ml/min. Its sensitivity, selectivity, accuracy and precision must be adequate for the bioavailabilty study of nicorandil, and the linearity ($r^2$ ≥ 0.9994) of nicorandil was also proved in the range of 0.05 ug/ml . 3 ug/ml. The pharmacokinetic parameters of nicorandil (5 mg) tablets were measured as the follow. AUC: 0.19 ug/ml·hr, $C_{max}$: 0.14 ug/ml, $t_{max}$: 0.58 hr, Ke: 0.11 hr., $t_{1/2\beta}$: 6.76 hrs. This method is simple and sensitive HPLC method using UV detector for determination of nicorandil in human plasma.