무코스타 정(레바미피드 100 mg) 에 대한 레바미드 정의 생물학적 동등성

조혜영,정현철,오인준,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus. to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, Mucosta^TM (Otsuka Korea Pharmaceutical Co., Ltd.) and Rebamide^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method at pH 6.8 dissolution media. Twenty normal male volunteers, 24.20±2.26 years in age and 66.19±9.41㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100㎎ of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 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. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Mucosta^TM were -2.57%, 5.77% and - 1.47%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 12.62% and 17.63% for AUC_t and C_max, respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t and C_max. were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ±20% (e.g., -9.96~4.82 and -4.54~16.09 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Rebamide^TM tablet is bioequivalent to Mucosta^TM tablet.

니세틸 정(아세틸-엘-카르니틴 500 mg)에 대한 엘카틴 정의 생물학적 동등성

조혜영,윤지훈,오인준,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Acetyl-L-camitine (ALC), an endogenous component of the L-carnitine family, is a naturally existing molecule synthesized from L-carnitine (LC) by carmtine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, Nicetile^TM (Dong-A Pharmaceutical Co.) and L-Cartin^TM (Kuhn Il Pharmaceutical Co.), according to the guidelines of Korea Food and Drug Administration (KFDA). The ALC release from the two ALC tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method in various dissolution media (pH 1.2, 6.0 and 6.8). Twenty six normal male volunteers, 24.46±3.67 years in age and 64.45±5.54 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 500㎎ of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. The dissolution profiles of the two ALC tablets were similar in all the dissolution media. The pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA 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 tablets were 0.35%, 0.93% and 2.34%, respectively, when calculated against the Nicetile^TM tablet. The powers (1-β) for AUC_t and C_max were 98.72% and 85.48%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.21% and 18.42% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -7.38~8.09 and -9.86~11.72 for AUC_t and C_max, respectively). These two parameters met the criteria of KFDA for bioequivalence, indicating that L-Cartin^TM tablet is bioequivalent to Nicetile^TM tablet.

아젭틴 정(염산아젤라스틴 1 mg)에 대한 아젤라 정의 생물학적 동등성

조혜영,윤지훈,서유리,오인준,이성관,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine H_1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, Azeptin^TM (Bu Kwang Pharmaceutical Co., Ltd.) and Azela^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 22.44±2.01 years in age and 61.99±6.18㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 1㎎ of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. 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 tablets were -6.45%, -2.60% and -7.14%, respectively, when calculated against the Azeptin^TM tablet. The powers (1-β) for AUC_t and C_max were 96.65% and 88.47%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 14.40% and 17.65% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -14.87∼1.97 and -12.92∼7.72 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Azela^TM tablet is bioequivalent to Azeptin^TM tablet.

니세틸 정(아세틸-엘-카르니틴 500 mg)에 대한 뉴로세틸 정의 생물학적 동등성

조혜영,김은아,정현철,심영순,임동구,오인준,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, Nicetiler^TM (Dong-A pharmaceutical Co., Ltd.) and Neurocetil^TM (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, 22.80±2.76 year in age and 63.07 7.98㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 500㎎ of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA 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 tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the Nicetile^TM tablet. The powers (1-β) for AUC_t and C_max were 94.87% and 87.17%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 15.58% and 19.16% AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -11.84∼6.41 and -10.57∼11.88 for AUC_t and C_max, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Neurocetil^TM tablet is bioequivalent to Nicetile^TM tablet.

리마틸 정(부시라민 100 mg)에 대한 부시린 정의 생물학적 동등성

조혜영,이문석,오인준,김동현,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, Rimatil^TM (Chong Kun Dang Pharmaceutical Co., Ltd.) and Bucilin^TM (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers. 23.67±2.09 years in age and 65.03±6.73㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After three tablets containing 100㎎ of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. 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_mex and T_max between two tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the Rimatil^TM tablet. The powers (1-β) for AUC_t and C_max were 84.31% and 91.16%, respectively. Minimum detectable differences (Δ) at α=0.10 and 1-β=0.8 were less than 20% (e.g., 18.58% and 16.51% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -12.77∼12.20 for AUC_t and -14.30∼7.90 for C_max). Two parameters met the criteria of KFDA for bioequivalence, indicating that Bucilin^TM tablet is bioequivalent to Rimatil^TM tablet.

딜라트렌 정(카르베딜롤 25 mg)에 대한 카베롤 정의 생물학적 동등성

조혜영,이문석,박순철,임동구,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

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 ⅦI 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±1.86 years in age and 64.81±4.56㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 25㎎ 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 (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.55% and 17.61% for AUC_t and C_max respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t and C_max were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ±20% (e.g., -5.69~10.16 and -12.30~8.30 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(l.25) (e.g., 0.95~1.11 and 0.89~1.09 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.

그란닥신 정(토피소팜 50mg)에 대한 토핌 정의 생물학적 동등성

조혜영,정현철,허수희,임동구,문재동,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.2

Tofisopam is a new type of tranquilizer valuable for the relief of anxiety and tension in a wide range of emotional disorders. Tofisopam has the therapeutic characteristics of a minor tranquilzer and a mild stimulatory effect. The purpose of the present study was to evaluate the bioequivalence of two tofisopam tablets, Grandaxin^TM (Hwan In Pharmaceutical Co., Ltd.) and Tofim^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 23.11±2.83 years in age and 65.43±7.64 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 50 mg of tofisopam was orally administered, blood was taken at predetermined time intervals and the concentrations of tofisopam in serum were determined using HPLC method with UV detector. 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 tablets based on the Grandaxin^TM were -5.59%, 2.22% and -13.18%, respectively. Minimum detectable differences (Δ) at α=0.10 and 1-β=0.8 were less than 20% (e.g., 14.95% and 19.34% for AUC_t and C_max respectively). The powers (1-β) at α=0.10, Δ=0.2 for AUC_t and C_max were 95.21% and 81.93%, respectively. The 90% confidence intervals were within ±20% (e.g., -15.64∼4.45 and -10.77∼15.21 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Tofim^TM tablet is bioequivalent to Grandaxin^TM tablet.

듀리세프 캅셀(세파드록실 500㎎)에 대한 하나세프 캅셀의 생물학적 동등성

조혜영,이석,문재동,이용복 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

Cefadroxil is a semi-synthetic cephalosporin active against many Gram-positive and Gram-negative bacteria. The drug has been used for the treatment of the urinary and respiratory tract infections when caused by susceptible strains of the designated microorganism. The purpose of the present study was to evaluate the bioequivalence of two cefadroxil capsules, Duricef (Bo Ryung Pharmaceutical Co. Ltd.) and Hanacef (Korean Pharmaceutical Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cefadroxil release from the two cefadroxil capsules 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, 21.58±2.43 years in age and 70.74±10.29 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one capsule containing 500 mg as cefadroxil was orally administered, blood was taken at predetermined time intervals and the concentrations of cefadroxil in serum were determined using HPLC with UV detector. The dissolution profiles of two cefadroxil capsules were very similar at all dissoluton 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 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 capsules based on the Duricef were 0.05%, -5.29% and 4.53%. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(l.25) (e.g., log(0.95)∼log(1.05) and log(0.87)∼log(l.02) for AUC_t, and C_max, respectively). The 90% confidence interval using untransformed data was within ±20% (e.g., -6.75∼15.74 for T_max). All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Hanacef capsule is bioequivalent to Duricef capsule.

체내동태 연구를 위한 혈청 중 펜톡시필린의 HPLC 정량법 개발 및 검증

조혜영,강현아,류희두,이화정,문재동,이용복 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.2

리마틸 정(부시라민 100㎎)에 대한 부시린 정의 생물학적 동등성

조혜영,이문석,오인준,김동현,문재동,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.2

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, Rimatil^TM (Chong Kun Dang Pharmaceutical Co., Ltd.) and Bucilin^TM (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 23.67±2.09 years in age and 65.03±6.73 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After three tablets containing 100 mg of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. 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 tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the Rimatil^TM tablet. The powers (1-β) for AUC_t and C_max were 84.31 % and 91.16%, respectively. Minimum detectable differences (Δ) at α=0.10 and 1-β=0.8 were less than 20% (e.g., 18.58% and 16.51% for AUC_t and C_max respectively). The 90% confidence intervals were within ±20% (e.g., -12.77∼12.20 for AUC_t and -14.30∼7.90 for C_max). Two parameters met the criteria of KFDA for bioequivalence, indicating that Bucilin^TM tablet is bioequivalent to Rimatil^TM tablet.