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.

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

조혜영,오인준,이용복,임동구,문재동,심영순,김은아,정현철 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.1

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, Nicetile^(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 (△) 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.

피부와 외래환자와 일반인의 진균질환 역학조사

문현주,문재동,이지범,김성진,원영호,이승철 全南大醫大 2001 전남의대학술지 Vol.37 No.4

직업병연구에 있어서 시간의존형 폭로변인의 의의

문재동 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.2

Although the final cumulative exposure has been used as a exposure variable on the cohort study for the relation between exposure and disease, the bias from the use of fixed exposure can be developed because the exposure amount changes across the time. We developed the program to handle the Cox model with irregularly changing time-dependent exposure variable and covariates, and the validity about the application of time-dependent exposure variable and lagged interval was practically evaluated by analyzing the data collected for typical retrospective cohort study with that program. The results were as follows : The exposure-response relations between the deaths from lung cancer and exposures(fixed or time-dependent) were not clear when 0 year lagged interval was applied. When 15 years lagged interval was applied, the exposure-response relations between the deaths from lung cancer and the time-dependent exposures to crystalline silica were observed and relative risks increased like 1.00, 1.17, 1.30 and 2.45 across the exposure levels. The relative risk estimates for lung cancer with time-dependent exposure variable were higher than those with fixed exposure variable without regard to the application of lagged interval. The exposure-response relations between the deaths from non-malignant respiratory disease(NMRD) and exposures (fixed or time-dependent) were observed across exposure levels when 0 year lagged interval was applied. When 15 years lagged interval was applied, the exposure-response relations between the deaths from NMRD and the time-dependent exposures to crystalling silica were observed, but were not with fixed exposure variable. The relative risk estimates for NMRD mortality with time-dependent exposure variable were higher than those with fixed exposure variable, and the application of lagged interval on the evaluation of NMRD mortality was meaningless. The results suggest that the application of time-dependent exposure variable on the study of exposure-effect relation should be considered and the application of lagged interval should be decided according to the time needed from disease detection to death.

굴루코파지 정(염산메트폴민 500mg)에 대한 그리코민 정의 생물학적 동등성

조혜영,문재동,이용복 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3

Metformin is an oral antihyprrglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve and increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablet, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin(Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, 23.78±1.96 years in age and 68.77±10.41㎏ in body weight, were divided into two groups with a randomized 2×2 cross-over study. After one tablet containing 500㎎ as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at all dissolution media. The pharmacokinetic parameters such as AUC_t C_max and T_max were calculated. The ANPVA test was performed for the statistical analysis of the logarithmically transformed AUC_t and C_max, untransformed T_max. The results showed that the differences in AIC_t, C_max and T_max between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, 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) ti log(1.25) (e.g.,log(0.94)∼log(1.09) and log(1.01)∼log(1.15) for AUC_t and C_max, respectively), indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

굴루코파지 정(염산메트폴민 500 mg)에 대한 그리코민 정의 생물학적 동등성

조혜영,문재동,이용복 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic does. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method with various dissolution media (pH1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, 23.75±1.96 years in age and 68.77±10.41 ㎏ in body weight, were divided into two groups with a randomized 2×2 cross-over study. After one tablet containing 500 ㎎ as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were dertermined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at all dissolution media. The pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed AUC_t and C_max untransformed T_max. The results showed that the differences in AUC_t, C_max and T_max 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(0.94) ∼log(1.09) and log (1.01) ∼log(1.15) for AUC_t, C_max, respectively), indicating that Glycomin tablets is bioequivalent to Glucophage tablet.

알기론 정(브롬화 시메트로피움 50 mg)에 대한 알피트 정의 생물학적 동등성

조혜영,문재동,이용복 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, Algiron™ (Boehringer Ingelheim Korea Ltd.) and Alpit™ (Hana Phamaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KDFA). The cimetropium bromide release from two cimetropium bromide 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 normal male volunteers, 25.25 ± 2.10 years in age and 65.76 ± 6.39 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After three tablets containing 50 ㎎ of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide 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 Algiron™ were 2.19%, -5.97% and 3.49%, respectively. Minimum differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.71%, 19.05% and 15.11% for AUC_t, C_max and T_max, respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t, C_max and T_max were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ±20% (e.g., -5.84∼10.21, -17.11∼5.18 and -5.35∼12.33 for AUC_t, C_max and T_max, respectively). There were no sequence effect between two tablets in logarithmically tanformed AUC_t, C_max. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., 0.94∼1.10 and 0.85∼1.05 for AUC_t, C_max, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that Alpit™ tablet is bioequivalent to Algiron™ tablet.

알기론 정(브롬화 시메트로피움 50 mg)에 대한 알피트 정의 생물학적 동등성

조혜영,이용복,문재동 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, Algiron^TM (Boehringer Ingelheim Korea Ltd.) and Alpit^TM (Hana Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The cimetropium bromide release from the two cimetropium bromide 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 normal male volunteers, 25.25±2.10 years in age and 65.76±6.39 kg in body weight, were divided into two groups and a randomized 2 × 2 cross-over study was employed. After three tablets containing 50 mg of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide 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 Algiron^TM were 2.19%, -5.97% and 3.49%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β-0.8 were less than 20% (e.g., 13.71 %, 19.05% and 15.11% for AUCt, C_max and T_max, respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t C_max and T_max were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within 20% (e.g., -5.84∼10.21, -17.11∼5.18 and -5.35∼12.33 for AUC_t C_max and T_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 data were within the acceptance range of log(0.8) to log(1.25) (e.g., 0.94-1.10 and 0.85-1.05 for AUC_t and C_max respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that Alpit^TM tablet is bioequivalent to Algiron^TM tablet.

프레탈 정(실로스타졸 100 mg)에 대한 엘지실로스타졸 정의 생물학적 동등성

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

Cilostazol has both antithrombotic and cerebral vasodilating effects, and one of the mechanism is the selective inhibition of platalet cyclic AMP phosphodiesterase. Bioequivalence of two cilostazol tablets, the Pletaal^TM (Korea Otsuka Pharmaceutical Co.) and the LG Cilostazol^TM (LG Chemical Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers (20∼29 years old) were randomly divided into two groups and a randomized 2×2 cross-over study was employed. After oral administration of Pletaal^TM or LG Cilostazol^TM tablet (100㎎ cilostazol), blood samples were taken at predetermined time intervals and the serum cilostazol concentrations were determined using an HPLC method with UV/VIS detector. The pharmacokinetic parameters (AUC_t, C_max and T_max) were calculated and ANOVA was utilized for the statistical analysis. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Pletaal^TM tablet were -5.39%, 2.32% and 4.26%, respectively. The powers (1-β) for AUC_t, C-max, and T_max were 83.81%, 96.02% and 91.04%, respectively. Minimum detectable differences (Δ) and 90% confidence intervals were all less than ±20%. All these parameters met the criteria of KFDA for bioequivalence, indicating that LG Cilostazol^TM tablet is bioequivalent to Pletaal^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.