흰쥐에서 트리플푸살의 위상관 및 간 초희통과효과

조혜영,정태진,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

In order to elucidate the influence of intestinal and hepatic first-pass effect on the pharmacokinetics of triflusal, the biotransformation of triflusal in the gastrointestinal tract and liver was designed. Moreover, we tried to establish an HPLC method applicable for bioassay and available to pharmacokinetics, not only with the simultaneous determination of triflusal and its active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), but also with improving sensitivity. After the administration of triflusal (10 mg/kg) and HTB (10 mg/kg) into femoral vein, portal vein (only triflusal) and oral route (only triflusal), pharmacokinetic parameters were investigated from the plasma concentration-time profiles of triflusal and HTB in rats. An HPLC method was developed for the simultaneous determination of triflusal and HTB in rat plasma, urine and bile. The HPLC analysis was carried out using a C18 column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The calibration curves were linear over the concentration range 0.05-5.0 ㎍/ml for triflusal and 0.2-200.0 ㎍/ml for HTB with correlation coefficients greater than 0.999 and with intra-day or inter-day coefficients of variation not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rats. It was supposed that triflusal was almost metabolized in vivo because urinary and biliary excreted amounts of triflusal could be ignored as it was lower than 1.2% of the administered dose. According to the gastrointestinal and hepatic biotransformation pathways of triflusal, it was found that triflusal was hydrolyzed by about 5% in intestine and metabolized by about 53% in liver, and that the bioavailability of triflusal after oral administration of triflusal was 0.44, and also that the fraction of total elimination rate of triflusal which formed HTB in liver (F_mi, %) was about 98%. These results showed that triflusal was almost metabolized in liver, and the total elimination of triflusal in the body was dependent to the formation rate of HTB from triflusal in liver.

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.

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.

흑두 추출물이 모발 주기 anagen 시기의 증식과 분화에 미치는 영향

조영롱,이은정,조경혜 서울여자대학교 2010 자연과학연구논문집 Vol.22 No.-

A hair follicle is one of complex miniorgans in human body which has a life cycle of anagen, catagen and telogen. The three stages occur periodically and it is reported that this cycle is controlled by the balance of Bmp and noggin. This study attempts to verify in a molecular level if a Glycine Semen nigra extract known as a hair restorer has positive effect on maintaining autonomous anagen stage of DP cells isolated from 1 day-old rat back skin by expressing Bmp and noggin. It was proven that the Glycine Semen nigra extract stimulates mRNA expression of bmp4, bmp6 and their receptor bmpr1a, which maintains anagen stage and stimulates differentiation. The effect of Glycine Semen nigra extract on stimulating differentiation of DP cells was also verified as the extract increases the expression of lef1 and other differentiation marker genes (wif1, akp2, alx4) for differentiation and the enzyme activity of alkaline phosphatase. It was observed that Glycine Semen nigra extract induces anagen phase and increases the gene expression of Bmp antagonist noggin which stimulates proliferation of DP cells. The expression of various growth factors (fos, vegf, fgf2) related to the proliferation of DP cell and hair follicle increases. The expression of wnt7a, which maintains anagen and stimulates cell multiplication, and its effector β-catenin also increased. Therefore, it was verified that Glycine Semen nigra extract has positive effect on hair growth by maintaining anagen stage, at which multiplication and differentiation of follicular cells actively occur. Glycine Semen nigra extract is expected to be used as a hair tonic or a hair growth promoter that maintains anagen stage and healthy hair.

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.

유한세프라딘 캅셀(세프라딘 500 mg)에 대한 브로드세프 캅셀의 생물학적 동등성

조혜영,이석,강현아,오인준,임동구,문재동,이용복 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Cepharadine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequinalence of two cepharadine capsules, Cefradine Yuhan (Yuhan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules ?? 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, 23.10±2.90 years in age and 67.69±8.04 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one capsule containing 500 ㎎ as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cepharadine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the phaemacokinetic 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 Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. 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(1.25) (e.g., log(0.93)∼log(1.02) and log(0.88)∼log(1.13) for AUC_t, and C_max, respectively). the 90% confidence interval using untransformed data was within ±20% (e.g., -17.54∼7.78 for T_max). All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.

그란닥신 정(토피소팜 50 mg)에 대한 토핌 정의 생물학적 동등성

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

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㎏ in body weight, were divided into two groups and a randomized 2 x 2 cross-over study was employed. After one tablet containing 50㎎ 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.

기초화장용 제품 중 크림과 로션제의 안정성 평가방법

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

This study was attempted to develop the physicochemical and morphological stability test methods for the cream and lotion formulations among the cosmetic foundations and to provide the guidance for the stability methods with respect to basic emulsions and creams. With these developed stability test methods, we can evaluate the expired date or life time of the available basic cosmetics, especially basic lotions and creams. Also, the stability test methods established in this study can be used as a guideline to test physical and morphological stability of cosmetics in the future. Thus, we selected two types of basic cosmetics such as lotions and creams made by four different cosmetic companies and applied them to stability test methods depending on the temperature changes such as temperature cycling and freezing-thawing cycling test. After the temperature changes, the conductivity, turbidity, particle size, creaming ratio and pH changes of the creams and lotions were evaluated and morphological changes such as crystal formation, oder, color and feeling of the creams and lotions were also tested. As the results of the stability tests, all the tested creams and lotions except for one lotion were stable. Therefore, it may be concluded that these short-term accelerated stability tests as physical stability test depending on the temperature change study were suitable for the stability testing methods for the basic cosmetics and may be useful for the establishment of the guideline for the stability test of cosmetics.

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.

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

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

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 levousulpiride 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 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 2.5 ㎎ of levousulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of lovosulpiride 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 in 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.