• Journal of Pharmaceutical Investigation
• /
• v.31 no.4
• /
• pp.289-295
• /
• 2001

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 VII 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, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg 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 $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ 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(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ 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.

• Journal of Life Science
• /
• v.24 no.8
• /
• pp.827-836
• /
• 2014

There is a rising trend in obesity due to various factors, including changes in eating habits, lack of exercise, and genetic and psychological factors. Citrus peel has been reported to prevent obesity via antioxidative, antihypertensive, and LDL cholesterol-lowering effects. This study investigated the effects of citrus peel extract fermented with or without Aspergillus oryzae in a mouse model of diet-induced obesity. The animals were divided into four groups: a high-fat diet group (HFD), a normal fat diet (NFD) group, a citrus peel extract (CP) group, and a citrus peel extract fermented with A. oryzae (CPA) group. The citrus peel extract improved lipid metabolism and weight loss in the high-fat diet-induced obese mouse model. As expected, the body weight was higher in the HFD group compared with the NFD, CP, and CPA groups. However, the concentrations of total cholesterol (TG) and triglyceride (TC) in the serum and liver of the CP and CPA groups were lower than in the HFD group. There were no significant differences in the HDL cholesterol concentration among the groups. Taken together, our results suggest that extract of citrus peel biotransformed with A. oryzae had more antiobesity activity than citrus peel not transformed by A. oryzae through the fermentation of metabolites.

• Journal of Life Science
• /
• v.20 no.5
• /
• pp.710-716
• /
• 2010

This study was conducted to investigate the effect of Makgeolli (MG) and Makgeolli GiGemi (MGG) on blood flow, serum lipid improvement in vivo, and inhibition of angiotensin converting enzyme (ACE) in vitro. The activities of serum AST and ALT were increased by ovariectomy. Serum AST levels were decreased to $77.71{\pm}13.97$ and $74.57{\pm}14.90\;unit/ml$ in the OVX-MG50 and OVX-MGG50 groups compared to the OVX-control group ($91.14{\pm}12.02\;unit/ml$). Serum ALT levels were decreased to $34.00{\pm}8.41$ and $30.43{\pm}3.60\;unit/ml$ in OVX-MG50 and OVX-MGG50 groups compared to the OVX-control group ($37.14{\pm}5.40\;unit/ml$). Serum total cholesterol and triglyceride contents decreased in the sham group compared with OVX-control group by ovariectomy. Six weeks feeding of MG and MGG resulted in a decrease to $116.14{\pm}36.02$ and $109.14{\pm}11.55\;mg/dl$ compared to the OVX-control group ($120.43{\pm}8.36\;mg/dl$) in serum total cholesterol, and triglyceride levels were decreased to $52.43{\pm}12.41$ and $47.29{\pm}12.08\;mg/dl$ in the OVX-MG50 and OVX-MGG50 groups compared to the OVX-control group ($58.57{\pm}5.47\;mg/dl$). The level of HDL-cholesterol in the OVX-control group was significantly reduced to $51.29{\pm}20.49\;mg/dl$ compared to the sham group ($72.29{\pm}10.29\;mg/dl$), but it was increased to $70.71{\pm}19.53$ and $62.00{\pm}20.20\;mg/dl$ with MG and MGG supplementation. Furthermore, the effect of the MG group was higher than the MGG group. Microscopic observation showed that whole blood passed smoothly through the micro channels in the MG and MGG supplemented groups. The platelet aggregation ability of the groups treated with MG and MGG was less than that of the OVX-control group. In vitro assay, the angiotensin converting enzyme (ACE) activity was significantly inhibited by MG and MGG (82.6% and 68.9% inhibition at 0.4 g/ml). These results suggest that the beneficial effects of MG and MGG may be used to improve on the lipid metabolic syndrome of menopausal women. In addition, MG and MGG might improve blood homeostasis mediated activities via antiplatelets and MG and MGG may be used as antihypertensive functional foods and nutraceuticals.