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.

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.

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.

Protective effect of Panicum dichotomiflorum in a rat model of testosterone-induced benign prostatic hyperplasia

Eun Bok Baek,Suyoung Park,Eun-Ju Hong,Warisraporn Tangchang,Hwa-Young Son,Hyo-Jung Kwon 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate gland, resulted from hyperplastic changes of prostate epithelial and stromal cells and it can be lead to lower urinary tract symptoms. Panicum dichotomiflorum (PD) is an annual grass distributing throughout the world. This study was aimed to evaluate the protective effect of PD extract on benign prostatic hyperplasia (BPH) in a rat model of testosterone-induced BPH. BPH of rat was induced by daily subcutaneous (s.c) administration of testosterone propionate (TP) 3 mg/kg for four weeks. Simultaneously, rats were also administered daily oral gavage of PD (150 mg/kg), finasteride (10 mg/kg) as a positive control or vehicle. After final treatment, all animals were sacrificed humanely and prostates of each animal were isolated, weighed and collected for further analysis. Administration of PD to testosterone-induced BPH rats notably reduced relative prostate weight and concentrations of prostatic dihydrotestosterone (DHT) and serum testosterone. Epithelial thickness and expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were markedly suppressed by PD treatment. In addition, protein expressions of the B-cell lymphoma 2 (Bcl-2) and cleaved caspase-3 were reduced PD-treated rats. PD decreased the levels of growth factors including transforming growth factor-beta1 (TGF-β1) and vascular endothelial growth factor (VEGF) and protein expression of phospho-Akt. Further investigation showed that PD suppressed testosterone-induced prostatic inflammation and inflammatory cytokines including tumor necrosis factor- α (TNF-α), interleukin (IL)-6 and IL-8. Taken together, PD protects from BPH progression by enhancing apoptosis and inhibiting growth factor signaling and inflammatory cytokines, suggesting that PD has potential to protect from BPH progression accompanied by inflammation.

Inhibition of Arterial Myogenic Responses by a Mixed Aqueous Extract of Salvia Miltiorrhiza and Panax Notoginseng (PASEL) Showing Antihypertensive Effects

Baek, Eun-Bok,Yoo, Hae-Young,Park, Su-Jung,Chung, Young-Shin,Hong, Eun-Kyung,Kim, Sung-Joon The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

The dried roots of Danshen (Salvia miltiorrhiza) and Sanchi (Panax notoginseng) have been widely used in traditional Chinese medicine for promoting blood circulation as well as various other bodily functions. Here we investigated the effects of a mixture of aqueous extracts of Danshen and Sanchi, named PASEL, on blood pressure and vascular contractility in rats. Orally administered PASEL (62.5 mg/kg and 250 mg/kg, for 5 weeks) lowered the blood pressure of spontaneous hypertensive rats (SHR) but this was not observed in normal Wistar-Kyoto rats (WKR). We then investigated the effects of PASEL on the arterial contraction of the small branches of cerebral arteries (CAs) and large conduit femoral arteries (FAs) in rats. PASEL did not affect high-K (KCI 60 mM)- or phenyleprine (PhE)-induced contracture of FAs. The myogenic response, a reactive arterial constriction in response to increased luminal pressure, of small CA was dose-dependently suppressed by PASEL in SHR as well as control rats. Interestingly, the KCI-induced contraction of small CAs was slowly reversed by PASEL, and this effect was more prominent in SHR than control WKR. PASEL did not inhibit angiotensin-converting enzyme (ACE) activity. These results demonstrated that the antihypertensive effect of PASEL might be primarily mediated by altering the arterial MR, not by direct inhibition of L-type $Ca^{2+}$ channels or by ACE inhibition.

Inhibition of Arterial Myogenic Responses by a Mixed Aqueous Extract of Salvia Miltiorrhiza and Panax Notoginseng (PASEL) Showing Antihypertensive Effects

Eun Bok Baek,Hae Young Yoo,Su Jung Park,Young-Shin Chung,Eun-Kyung Hong,Sung Joon Kim 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

The dried roots of Danshen (Salvia miltiorrhiza) and Sanchi (Panax notoginseng) have been widely used in traditional Chinese medicine for promoting blood circulation as well as various other bodily functions. Here we investigated the effects of a mixture of aqueous extracts of Danshen and Sanchi, named PASEL, on blood pressure and vascular contractility in rats. Orally administered PASEL (62.5 mg/kg and 250 mg/kg, for 5 weeks) lowered the blood pressure of spontaneous hypertensive rats (SHR) but this was not observed in normal Wistar-Kyoto rats (WKR). We then investigated the effects of PASEL on the arterial contraction of the small branches of cerebral arteries (CAs) and large conduit femoral arteries (FAs) in rats. PASEL did not affect high-K (KCl 60 mM)- or phenyleprine (PhE)-induced contracture of FAs. The myogenic response, a reactive arterial constriction in response to increased luminal pressure, of small CA was dose-dependently suppressed by PASEL in SHR as well as control rats. Interestingly, the KCl-induced contraction of small CAs was slowly reversed by PASEL, and this effect was more prominent in SHR than control WKR. PASEL did not inhibit angiotensin-converting enzyme (ACE) activity. These results demonstrated that the antihypertensive effect of PASEL might be primarily mediated by altering the arterial MR, not by direct inhibition of L-type Ca²⁺ channels or by ACE inhibition.

Differential recruitment of mechanisms for myogenic responses according to luminal pressure and arterial types

Baek, Eun Bok,Jin, Chunzi,Park, Su Jung,Park, Kyung Sun,Yoo, Hae Young,Jeon, Ju Hong,Earm, Yung E.,Kim, Sung Joon Springer-Verlag 2010 Pfl ugers Arch Vol.460 No.1

Protective effect of Gyeji-tang in a mouse model of cigarette smoke and lipopolysaccharide-induced chronic obstructive pulmonary disease

Eun Bok Baek,Jin-hyung Rho,Eun-Ju Hong,Hyo-Jung Kwon 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder that is characterized by persistent airflow limitation and associated with symptoms of shortness of breath, cough, and sputum production. Gyeji-tang (GJT) is composed of five oriental herb and widely used as a traditional Asian medicine. In this study, we examined the protective effect of GJT in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS). Mice received CS exposure daily for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. GJT (100 and 200 mg/kg) was administrated daily 1 hour before CS treatment for the last 4 weeks. Roflumilast (10 mg/kg) as a positive control was used in this study. In histopathological evaluation, bronchoalveolar structural damage with inflammations were significantly suppressed in GJT treated animals. Administration of GJT significantly suppressed influx of total inflammatory cells, especially macrophages in BALF induced by CS with LPS exposure. Relative expression of TNF-α, IL-6, L-1β and IL-8 were significantly inhibited in lung tissues by treatment of GJT. GJT prevented activation of NF-κB and STAT3 induced by CS and LPS. Furthermore, GJT treatment decreased the expression of structural remodeling markers including transforming growth factor beta (TGF-β), matrix metallopeptidase (MMP)-7 and MMP-9. Present study results demonstrates that GJT prevents lung inflammation and airway remodeling induced by CS with LPS exposure via NF-κB and STAT3 pathway. Therefore, GJT may be potential therapy for the treatment of COPD.

Inhibition of Microglia-Derived Oxidative Stress by Ciliary Neurotrophic Factor Protects Dopamine Neurons In Vivo from MPP ⁺ Neurotoxicity

Baek, Jeong Yeob,Jeong, Jae Yeong,Kim, Kyoung In,Won, So-Yoon,Chung, Young Cheul,Nam, Jin Han,Cho, Eun Ju,Ahn, Tae-Beom,Bok, Eugene,Shin, Won-Ho,Jin, Byung Kwan MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.11

<P>We demonstrated that capsaicin (CAP), an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), inhibits microglia activation and microglia-derived oxidative stress in the substantia nigra (SN) of MPP<SUP>+</SUP>-lesioned rat. However, the detailed mechanisms how microglia-derived oxidative stress is regulated by CAP remain to be determined. Here we report that ciliary neurotrophic factor (CNTF) endogenously produced by CAP-activated astrocytes through TRPV1, but not microglia, inhibits microglial activation and microglia-derived oxidative stress, as assessed by OX-6 and OX-42 immunostaining and hydroethidine staining, respectively, resulting in neuroprotection. The significant increase in levels of CNTF receptor alpha (CNTFRα) expression was evident on microglia in the MPP<SUP>+</SUP>-lesioned rat SN and the observed beneficial effects of CNTF was abolished by treatment with CNTF receptor neutralizing antibody. It is therefore likely that CNTF can exert its effect via CNTFRα on microglia, which rescues dopamine neurons in the SN of MPP<SUP>+</SUP>-lesioned rats and ameliorates amphetamine-induced rotations. Immunohistochemical analysis revealed also a significantly increased expression of CNTFRα on microglia in the SN from human Parkinson’s disease patients compared with age-matched controls, indicating that these findings may have relevance to the disease. These data suggest that CNTF originated from TRPV1 activated astrocytes may be beneficial to treat neurodegenerative disease associated with neuro-inflammation such as Parkinson’s disease.</P>