무코스타정(레바미피드 100mg)에 대한 레바미드 정의 생물학적 동등성

조혜영,정현철,오인준,문재동,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

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 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100 mg 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.

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.

아마릴 정(글리메피리드 2㎎)에 대한 글리메드 정의 생물학적 동등성

조혜영,박은자,강현아,백승희,이석,김세미,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tables, Amaryl^(?)(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±2.19 years in age and 66.55±8.85 kg in body weight, were divided into two groups and randomized 2×2 cross-over study was employed. After one tablet containing 2 ㎎ 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 detctor. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as 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)∼log(1.04) and log(0.82)∼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.

스프렌딜 지속정(펠로디핀 5㎎)에 대한 스타핀 지속정의 생물학적동등성

조혜영,강현아,이석,백승희,박은자,최후균,문재동,이용복 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4

Felodipine is a calcium antagonist that lowers blood pressure by reducing peripheral resistance by means of a direct, selective action on smooth muscle in arterial resistance vessels. Furthermore, it have been approved for the effective in angina pectoris and cardiac failure. The purpose of the present study was to evaluate the bioequivalence of two felodipine extended release (ER) tablets, Splendil (YuHan Corporation) and Stapin (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). THe felodipine release from the two felodipine formulations in vitro was tested using KP Ⅷ Apparatus Ⅱ method at pH 6.5 buffer solution. Twenty six healthy male subjects, 22.73±1.78 years in age and 66.66±7.28 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 5 ㎎ as felodipine were orally administered, blood sample was taken at predetermined time intervals and the concentrations of felodipine in serum were determined using column-switching HPLC method with UV detector. The dissolution profiles of two formulations were similar at pH 6.5 buffer solution. Besides, the pharmacokinetic parameters such as AUG_(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 between two formulations based on the Splendil were 2.53%, 1.32% and 18.32% for AUC_(t), C_(max) and T_(mzx), 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(0.86)∼log(1.20) and long(0.89)∼long(1.23) for AUC_(t) and C_(max), respectively). Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Stapin ER tablet and Splendil ER tablet are bioequivalent.

레보프라이드 정(레보설피리드 25㎎)에 대한 레보피드 정의 생물학적 동등성

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

Levosulpiride is the levo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic D_2 receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequivalence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride 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 eight normal male volunteers, 23.82±3.26 years in age and 69.13±8.58 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride 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 Levopride were -1.17%, 1.20% and -1.09%, 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(0.93)∼log(1.07) and log(0.90)∼log(1.14) for AUC_t and C_max, respectively). The 90% confidence interval using untransformed data was within ±20% (e.g., -19.47∼16.20 for T_max). All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

시클러 캡슐(세파클러 250㎎)에 대한 경보세파클러 캡슐의 생물학적동등성

조혜영,강현아,김세미,박찬호,오인준,임동구,문재동,이용복 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

The purpose of the present study was to evaluate the bioequivalence of two cefaclor capsules, Ceclor (Lilly Korea Co., Ltd.) and Kyongbocefaclor (Kyongbo Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of cefaclor from the two cefaclor 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 four healthy male subjects. 22.96±1.52 years in age and 67.03±7.90 kg in body weight, were divided into two groups and a randomized 2x2 cross-over study was employed. After one capsule containing 250 mg of cefaclor was orally administered, blood was taken at pre-determined time intervals and the concentrations of cefaclor in serum were determined using HPLC method with UV 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 Tmaa. The results showed that the differences between two formulations based on the reference drug, Ceclor. were -1.90%, 2.68% and -7.60% for AUCt, 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-log 1.06 and log 0.92-log 1.18 for AU', and C_(max), respectively). Thus. the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kyongbocefaclor capsule was bioequivalent to Ceclor capsule.

비유피-4 정(염산프로피베린 20㎎)에 대한 건일염산프로피베린 정의 생물학적동등성

조혜영,박은자,강현아,백승희,김세미,박찬호,오인준,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.5

The purpose of the present study was to evaluate the bioequivalence of two propiverine hydrochloride tablets. BUP-4 (Jeil Pharm. Co., Ltd.) and Kuhnil Propiverine Hydrochloride (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The propiverine release from the two propiverine hydrochloride 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 solutions, water and blend of polysorbate 80 into pH 6.8). Twenty six healthy male subjects, 23.73 ± 2.79 years in age and 67.04 ± 7.93 kg in body weight, were divided into two groups and a randomized 2 x 2 cross-over study was employed. After one tablet containing 20 mg as propiverine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of propiverine in serum were determined using HPLC method with UV detector. The dis-solution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC" C _(max) and T _(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC, C_(max), and untransformed T_(max). The results showed that the differences between two formulations based on the BUP-4 were 0.17%, 7.98% and 4.55% for AUC,, C_(max), and respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically trans-formed data were within the acceptance range of log(0.8) to log(1.25) (e.g., log(0.88)-log(l .12) and log(0.90)-log(l.15) for AUC, and _(max), respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kuhnil Propiverine Hydrochloride tablet was bioequivalent to BUP-4 tablet.

리스페달 정(리스페리돈 2㎎)에 대한 리스펜 정의 생물학적 동등성

조혜영,박은자,강현아,백승희,이석,박찬호,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

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 risperione 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 butter solution and water). Twenty four healthy male subjects, 23.33±2.10 years in age and 69.24±8.05 kg in body weight, were divided into two groups and a randomized 2×2 crossover study was employed. After one tablet containing 2 ㎎ as risperidone was orally administered, blood was taken at predetermined time intervals and the concentration 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) 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 Risperdal were 0.20, -1.29 and -11.09% 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(0.90)∼log(1.03) and log(0.84)∼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.

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.

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.